Endothelial-to-Mesenchymal Transition: Molecular Mechanisms of Induction and Regulation
Main Article Content
Abstract
Endothelial-to-mesenchymal transition (EndoMT) is a form of cellular transdifferentiation essential for cardiovascular development but now recognized as a driver of vascular dysfunction in numerous adult diseases. It is also increasingly appreciated as a mechanistic link between endothelial injury, fibrosis, and immune dysregulation observed in many of these pathologies. However, the exact events leading up to the induction and maintenance of EndoMT remain the subject of continued research. In this review, we discuss the numerous triggers of EndoMT identified to date as well as the pathways contributing to a persistent mesenchymal phenotype. Potential future directions are highlighted with an eye toward pharmacologic reversal of EndoMT and restoration of endothelial function.
Keywords:
Endothelial-to-mesenchymal transition (EndoMT), Fibrosis, Endothelial dysfunction, TGF-β signaling, Cellular transdifferentiation, Vascular disease, Molecular pathways, Therapeutic targets
Article Details
How to Cite
BARBI, Nicholas; PIERA-VELAZQUEZ, Sonsoles; JIMENEZ, Sergio A..
Endothelial-to-Mesenchymal Transition: Molecular Mechanisms of Induction and Regulation.
Medical Research Archives, [S.l.], v. 14, n. 4, may 2026.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/7461>. Date accessed: 22 may 2026.
doi: https://doi.org/10.18103/mra.v14i4.7461.
Keywords
Endothelial Cell, Endo-MT, Collagen, Fibrosis, Fiboblast, TGF-beta
Section
Review Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
1. JC K, N M, M T, M B, V F. Epithelial-to-mesenchymal and endothelial-to-mesenchymal transition: from cardiovascular development to disease. Circulation. 2012;125(14):1795-808.
2. S P, SA J. Endothelial to Mesenchymal Transition: Role in Physiology and in the Pathogenesis of Human Diseases. Physiol Rev. 2019;99(2):1281-1324.
3. X L, J G, PA D, H Y. Endothelial-to-mesenchymal transition: Pathogenesis and therapeutic targets for chronic pulmonary and vascular diseases. Biochem Pharmacol. 2019;168:100-107.
4. SA J, S P. Endothelial to mesenchymal transition (EndoMT) in the pathogenesis of Systemic Sclerosis-associated pulmonary fibrosis and pulmonary arterial hypertension. Myth or reality?. Matrix Biol. 2016;51:26-36.
5. I M, A B, R C, et al. Oxidative stress mediates the conversion of endothelial cells into myofibroblasts via a TGF-β1 and TGF-β2-dependent pathway. Lab Invest. 2014;94(10):1068-82.
6. Y L, Y X, Y S, et al. Exosomes derived from adipose tissue-derived stem cells alleviated H(2)O(2)-induced oxidative stress and endothelial-to-mesenchymal transition in human umbilical vein endothelial cells by inhibition of the mir-486-3p/Sirt6/Smad signaling pathway. Cell Biol Toxicol. 2024;40(1):39.
7. GR D, CG S. Endothelial NADPH oxidases: which NOX to target in vascular disease?. Trends Endocrinol Metab. 2014;25(9):452-63.
8. THG P, AM P, R G, et al. NADPH Oxidase-Derived Reactive Oxygen Species Generation Drives Endothelial-to-Mesenchymal Transition in Human Pulmonary Endothelial Cells Exposed to Sera From Patients With Idiopathic Pulmonary Fibrosis. J Cardiovasc Pharmacol. 2026;87(1):28-39.
9. X C, X X, T D, Z L, L D, H Z. Trimetazidine Reduces Cardiac Fibrosis in Rats by Inhibiting NOX2-Mediated Endothelial-to-Mesenchymal Transition. Drug Des Devel Ther. 2022;16:2517-2527.
10. S P, A M, SA J. Increased expression of NAPDH oxidase 4 in systemic sclerosis dermal fibroblasts: regulation by transforming growth factor β. Arthritis Rheumatol. 2015;67(10):2749-58.
11. F G, Y Z, B Z, et al. SESN1 attenuates the Ox‑LDL‑induced inflammation, apoptosis and endothelial‑mesenchymal transition of human umbilical vein endothelial cells by regulating AMPK/SIRT1/LOX1 signaling. Mol Med Rep. 2022;25(5):pii: 161. doi: 10.3892/mmr.2022.12678.
12. J X, H K, Y Y, et al. A Metabolic Basis for Endothelial-to-Mesenchymal Transition. Mol Cell. 2018;69(4):689-698.e7.
13. E A, F M, S P, et al. Glycolysis-derived acidic microenvironment as a driver of endothelial dysfunction in systemic sclerosis. Rheumatology (Oxford). 2021;60(10):4508-4519.
14. LJ C, JY L, P N, et al. Single-cell RNA sequencing unveils unique transcriptomic signatures of endothelial cells and role of ENO1 in response to disturbed flow. Proc Natl Acad Sci U S A. 2024;121(5):e2318904121.
15. C L, M L, W W, Y L, Z H, Z X. RNA-seq and ChIP-seq reveal microplastics induce endothelial-mesenchymal transition via HK2-mediated histone lactylation in pulmonary hypertension. Vascul Pharmacol. 2026;162:107571.
16. D Z, Z T, H H, et al. Metabolic regulation of gene expression by histone lactylation. Nature. 2019;574(7779):575-580.
17. X H, W C, M Y, M L, X L, S O. IGFBP5 promotes EndoMT and renal fibrosis through H3K18 lactylation in diabetic nephropathy. Cell Mol Life Sci. 2025;82(1):215.
18. SH C, ZY H, JK N, et al. A Hypoxia-Induced Vascular Endothelial-to-Mesenchymal Transition in Development of Radiation-Induced Pulmonary Fibrosis. Clin Cancer Res. 2015;21(16):3716-26.
19. M D, J M, L B, BL C, A V. Differential effect of hypoxia on early endothelial-mesenchymal transition response to transforming growth beta isoforms 1 and 2. Microvasc Res. 2016;108:48-63.
20. X X, X T, B T, E S, M Z, EM Z. Snail Is a Direct Target of Hypoxia-inducible Factor 1α (HIF1α) in Hypoxia-induced Endothelial to Mesenchymal Transition of Human Coronary Endothelial Cells. J Biol Chem. 2015;290(27):16653-64.
21. T S, EJ C, MH T, et al. Isolation and characterization of endothelial-to-mesenchymal transition cells in pulmonary arterial hypertension. Am J Physiol Lung Cell Mol Physiol. 2018; 314(1):L118-L126.
22. S S, M Z, Z Y, et al. The role of PDGF-B/TGF-β1/neprilysin network in regulating endothelial-to-mesenchymal transition in pulmonary artery remodeling. Cell Signal. 2016;28(10):1489-501.
23. H T, A B, KM M, et al. Endothelial HIF-2α contributes to severe pulmonary hypertension due to endothelial-to-mesenchymal transition. Am J Physiol Lung Cell Mol Physiol. 2018;314(2):L256-L275.
24. Y Z, K Y, Z Z, et al. The HIF2α-dependent upregulation of SETDB1 facilitates hypoxia-induced functional and phenotypical changes of pulmonary microvascular endothelial cells. Am J Physiol Cell Physiol. 2025;328(1):C40-C55.
25. Y L, J Z, B L, et al. RUNX3 modulates hypoxia-induced endothelial-to-mesenchymal transition of human cardiac microvascular endothelial cells. Int J Mol Med. 2017;40(1):65-74.
26. I S, M P, J H, R S, G E. Endothelial Mesenchymal Transition in Hypoxic Microvascular Endothelial Cells and Paracrine Induction of Cardiomyocyte Apoptosis Are Mediated via TGFβ₁/SMAD Signaling. Int J Mol Sci. 2017;18(11):doi: 10.3390/ ijms18112290.
27. H Z, Y L, L Y, et al. Bone morphogenetic protein-7 inhibits endothelial-mesenchymal transition in pulmonary artery endothelial cell under hypoxia. J Cell Physiol. 2018;233(5):4077-4090.
28. L L, J C, L S, Y X. RhoJ promotes hypoxia induced endothelial-to-mesenchymal transition by activating WDR5 expression. J Cell Biochem. 2018;119(4):3384-3393.
29. R T, Q L, L L, et al. Angiotensin II mediates the high-glucose-induced endothelial-to-mesenchymal transition in human aortic endothelial cells. Cardiovasc Diabetol. 2010;9:31.
30. RN T, LL L, JD Z, et al. Effects of angiotensin II receptor blocker on myocardial endothelial-to-mesenchymal transition in diabetic rats. Int J Cardiol. 2013;162(2):92-9.
31. Y C, B F, S C, Y C, S C. Mechanisms of endothelial to mesenchymal transition in the retina in diabetes. Invest Ophthalmol Vis Sci. 2014; 55(11):7321-31.
32. Y C, Q Y, Y Z, J K, P L, J H. The role of miR-328 in high glucose-induced endothelial-to-mesenchymal transition in human umbilical vein endothelial cells. Life Sci. 2018;207:110-116.
33. CH Y, Suriguga, M G, et al. High glucose induced endothelial to mesenchymal transition in human umbilical vein endothelial cell. Exp Mol Pathol. 2017;102(3):377-383.
34. H P, Y L, C W, et al. ROCK1 Induces Endothelial -to-Mesenchymal Transition in Glomeruli to Aggravate Albuminuria in Diabetic Nephropathy. Sci Rep. 2016;6:20304.
35. J Z, S C, H X, et al. S1PR2/Wnt3a/RhoA/ ROCK1/β-catenin signaling pathway promotes diabetic nephropathy by inducting endothelial mesenchymal transition and impairing endothelial barrier function. Life Sci. 2023;328:121853.
36. C F, Y L, J C, et al. Apelin Alleviated Endothelial-To-Mesenchymal Transition via Increasing BKCa in Diabetic Nephropathy. FASEB J. 2025;39(12):e70747.
37. Z M, W S, L Y, et al. Bach1 modulates AKT3 transcription to participate in hyperglycaemia-mediated EndMT in vascular endothelial cells. Clin Exp Pharmacol Physiol. 2023;50(6):443-452.
38. Y T, Z B, S G, B Y, W H. STAT5A modulated EndMT via upregulation of ELTD1 expression in diabetic nephropathy. Clin Exp Pharmacol Physiol. 2022;49(6):686-695.
39. L L, M Z, Q W, Z S, X C, C M. Sirt7/HIC1 complex participates in hyperglycaemia-mediated EndMT via modulation of SDC1 expression in diabetic kidney disease and metabolic memory. J Cell Mol Med. 2024;28(9):e18336.
40. M W, Y H, X W, et al. SirT7-mediated transcription of fascin in hyperglycemic glomerular endothelial cells contributes to EndMT in diabetic nephropathy. Acta Biochim Biophys Sin (Shanghai). 2024;56(4):586-596.
41. X L, L L, W H, et al. The SETD8/ELK1/bach1 complex regulates hyperglycaemia-mediated EndMT in diabetic nephropathy. J Transl Med. 2022;20(1):147.
42. SM W, JN T. Adaptation of the endothelium to fluid flow: in vitro analyses of gene expression and in vivo implications. Vasc Med. 2004;9(1):35-45.
43. Y F, D W, KG B. Mechanosensing and Mechanoregulation of Endothelial Cell Functions. Compr Physiol. 2019;9(2):873-904.
44. BJ B, A D, E E, A L. Shear stress and the endothelium. Kidney Int Suppl. 1998;67:S100-8.
45. KS C, AI G. The role of shear stress in the pathogenesis of atherosclerosis. Lab Invest. 2005; 85(1):9-23.
46. GJ M, CM F, Q C, JT B. Effects of shear stress pattern and magnitude on mesenchymal transformation and invasion of aortic valve endothelial cells. Biotechnol Bioeng. 2014;111(11):2326-37.
47. MM M, J S, S F, et al. Shear stress induces endothelial-to-mesenchymal transition via the transcription factor Snail. Sci Rep. 2017;7(1):3375.
48. K Z, W L, DD G, et al. Hydrogen sulfide attenuates atherosclerosis induced by low shear stress by sulfhydrylating endothelium NFIL3 to restrain MEST mediated endothelial mesenchymal transformation. Nitric Oxide. 2024;142:47-57.
49. A L, L T, S Z, J T, Z W, D W. Low shear stress-induced endothelial mesenchymal transformation via the down-regulation of TET2. Biochem Biophys Res Commun. 2021;545:20-26.
50. H D, MA S. High Fluid Shear Stress Inhibits Cytokine-Driven Smad2/3 Activation in Vascular Endothelial Cells. J Am Heart Assoc. 2022; 11(14):e025337.
51. T S, JR M, YH C, et al. High Shear Stress Reduces ERG Causing Endothelial-Mesenchymal Transition and Pulmonary Arterial Hypertension. Arterioscler Thromb Vasc Biol. 2025;45(2):218-237.
52. JR M, ES L, M S, et al. Endothelial-to-mesenchymal transition contributes to fibro-proliferative vascular disease and is modulated by fluid shear stress. Cardiovasc Res. 2015;108(3):377-86.
53. K CL, A S, V B, et al. Shear Stress Alterations Activate BMP4/pSMAD5 Signaling and Induce Endothelial Mesenchymal Transition in Varicose Veins. Cells. 2021;10(12):doi: 10.3390/cells10123563.
54. NA O, X H, IP D, et al. Abnormal Flow Conditions Promote Endocardial Fibroelastosis Via Endothelial-to-Mesenchymal Transition, Which Is Responsive to Losartan Treatment. JACC Basic Transl Sci. 2021;6(12):984-999.
55. E K, M P, S C, et al. The interleukin-1 receptor type-1 in disturbed flow-induced endothelial mesenchymal activation. Front Cardiovasc Med. 2023;10:1190460.
56. CL K, V V, BJ S, et al. Oscillatory shear stress modulates Notch-mediated endothelial mesenchymal plasticity in cerebral arteriovenous malformations. Cell Mol Biol Lett. 2023;28(1):22.
57. S A, CL K, BJ S, SR K, S S. Altered venous flow drives endothelial to mesenchymal transition in varicose veins by suppressing PIEZO1-KLF2 signaling. Cell Mol Life Sci. 2025;82(1):345.
58. Collaborators G2RF. Global burden and strength of evidence for 88 risk factors in 204 countries and 811 subnational locations, 1990-2021: a systematic analysis for the Global Burden of Disease Study 2021. Lancet. 2024;403(10440): 2162-2203.
59. CJ W, RJ S, KC P, et al. Exposure to Ambient Particulate Matter Is Associated With Accelerated Functional Decline in Idiopathic Pulmonary Fibrosis. Chest. 2018;153(5):1221-1228.
60. B L, Y H, Y Y, X W, G L, W J. Atmospheric fine particulate matter (PM(2.5)) induces pulmonary fibrosis by regulating different cell fates via autophagy. Sci Total Environ. 2024;923:171396.
61. K M, C L, J X, et al. LncRNA Gm16410 regulates PM(2.5)-induced lung Endothelial-Mesenchymal Transition via the TGF-β1/Smad3/p-Smad3 pathway. Ecotoxicol Environ Saf. 2020;205:111327.
62. Q S, M W, L L, et al. PM(2.5) Induce Endothelial-Mesenchymal Transition and Cardiac Fibrosis via the NCOA4-Mediated Ferritinophagy. Adv Sci (Weinh). 2025;12(45):e07536.
63. JH P, JY C, GY K, M K, SH P, YH K. Endothelial BACE1, regulating the endothelial-to-mesenchymal transition (EndMT) induced by particulate matter (PM), is associated with cerebrovascular disease: Involvement of endothelial BACE1 in BBB disruption caused by diabetes. Free Radic Biol Med. 2026;243:96-110.
64. CH H, A M. Role of Smads in TGFβ signaling. Cell Tissue Res. 2012;347(1):21-36.
65. J M, G S, MJ G, P TD. TGF-β-Induced Endothelial to Mesenchymal Transition in Disease and Tissue Engineering. Front Cell Dev Biol. 2020;8:260.
66. H S, A V, PR S. Isoform-specific effects of transforming growth factor β on endothelial-to-mesenchymal transition. J Cell Physiol. 2018; 233(11):8418-8428.
67. M M, R D, K M. TGF-β and the TGF-β Family: Context-Dependent Roles in Cell and Tissue Physiology. Cold Spring Harb Perspect Biol. 2016;8(5):doi: 10.1101/cshperspect.a021873.
68. BC C, J N, J M, et al. TGF-β signaling mediates endothelial-to-mesenchymal transition (EndMT) during vein graft remodeling. Sci Transl Med. 2014;6(227):227ra34.
69. J M, G VDZ, MAFV G, et al. TGF-β-Induced Endothelial to Mesenchymal Transition Is Determined by a Balance Between SNAIL and ID Factors. Front Cell Dev Biol. 2021;9:616610.
70. D M, S P, R K. Transforming growth factor-β2 promotes Snail-mediated endothelial-mesenchymal transition through convergence of Smad-dependent and Smad-independent signalling. Biochem J. 2011;437(3):515-20.
71. L C, H S, Z T, et al. DUSP22 Ameliorates Endothelial-to-Mesenchymal Transition in HUVECs through Smad2/3 and MAPK Signaling Pathways. Cardiovasc Ther. 2024;2024:5583961.
72. R K, W C. Endothelial-to-Mesenchymal Transition in Health and Disease: Molecular Insights and Therapeutic Implications. Int J Mol Sci. 2025;26(23):doi: 10.3390/ijms262311724.
73. T F, M I, T I. A ROCK inhibitor suppresses the transforming growth factor-beta-2-induced endothelial-mesenchymal transition in Schlemm's canal endothelial cells. Sci Rep. 2023;13(1):9655.
74. Z L, SA J. Protein kinase Cδ and c-Abl kinase are required for transforming growth factor β induction of endothelial-mesenchymal transition in vitro. Arthritis Rheum. 2011;63(8):2473-83.
75. R N, H C. Wnt/β-Catenin Signaling, Disease, and Emerging Therapeutic Modalities. Cell. 2017; 169(6):985-999.
76. O A, M R, S R, N A, I F, AK H. Experimental myocardial infarction triggers canonical Wnt signaling and endothelial-to-mesenchymal transition. Dis Model Mech. 2011;4(4):469-83.
77. L L, L C, J Z, et al. C3a and C5a receptor antagonists ameliorate endothelial-myofibroblast transition via the Wnt/β-catenin signaling pathway in diabetic kidney disease. Metabolism. 2015; 64(5):597-610.
78. AV G, MS E, S D, et al. TGF-β1, pSmad-2/3, Smad-7, and β-Catenin Are Augmented in the Pulmonary Arteries from Patients with Idiopathic Pulmonary Fibrosis (IPF): Role in Driving Endothelial-to-Mesenchymal Transition (EndMT). J Clin Med. 2024;13(4):doi: 10.3390/jcm13041160.
79. X S, J F, F Y, et al. Diffuse Large B-Cell Lymphoma Promotes Endothelial-to-Mesenchymal Transition via WNT10A/Beta-Catenin/Snail Signaling. Front Oncol. 2022;12:871788.
80. M S, Y F, J W, Y Y, F Y. CXCR7 Inhibits Fibrosis via Wnt/β-Catenin Pathways during the Process of Angiogenesis in Human Umbilical Vein Endothelial Cells. Biomed Res Int. 2020;2020:1216926.
81. Z W, Z W, L G, et al. miR-222 inhibits cardiac fibrosis in diabetic mice heart via regulating Wnt/β-catenin-mediated endothelium to mesenchymal transition. J Cell Physiol. 2020;235(3):2149-2160.
82. AR K, JL K, Y K, S K, SC O, JK P. A novel RIP1-mediated canonical WNT signaling pathway that promotes colorectal cancer metastasis via β -catenin stabilization-induced EMT. Cancer Gene Ther. 2023;30(10):1403-1413.
83. SH W, JS C, JR H, et al. Tumour cell-derived WNT5B modulates in vitro lymphangiogenesis via induction of partial endothelial-mesenchymal transition of lymphatic endothelial cells. Oncogene. 2017; 36(11):1503-1515.
84. ZY Z, C Z, XY Y, HB L, LL W, L L. Knockdown of CD146 promotes endothelial-to-mesenchymal transition via Wnt/β-catenin pathway. PLoS One. 2022;17(8):e0273542.
85. M L, H D, NL J, et al. Dickkopf-3 in aberrant endothelial secretome triggers renal fibroblast activation and endothelial-mesenchymal transition. Nephrol Dial Transplant. 2019;34(1):49-62.
86. Y W, L S, X J, M Y, W X. miR-29 inhibits endothelial-to-mesenchymal transition in pulmonary hypertension of the newborn by regulating LRP6. FASEB J. 2025;39(7):e70502.
87. Z A, Y N, LSA P, et al. Wnt Site Signaling Inhibitor Secreted Frizzled-Related Protein 3 Protects Mitral Valve Endothelium From Myocardial Infarction-Induced Endothelial-to-Mesenchymal Transition. J Am Heart Assoc. 2022;11(7):e023695.
88. Y F, Z C, Z X, et al. Osteoglycin silencing exerts inhibitory effects on myocardial fibrosis and epithelial/endothelial-mesenchymal transformation in a mouse model of myocarditis. Biofactors. 2020; 46(6):1018-1030.
89. W W, S C, Z X, et al. von Willebrand Factor Deficiency Inhibits Endothelial-to-Mesenchymal Transition to Attenuate Pulmonary Fibrosis. Am J Respir Cell Mol Biol. 2025;73(6):906-919.
90. EJ D, LY C, KS A, et al. Inflammation and DKK1-induced AKT activation contribute to endothelial dysfunction following NR2F2 loss. Am J Physiol Lung Cell Mol Physiol. 2023;324(6):L783-L798.
91. SL C, JS S, A B, K K, DA T. Dkk1 and MSX2-Wnt7b signaling reciprocally regulate the endothelial-mesenchymal transition in aortic endothelial cells. Arterioscler Thromb Vasc Biol. 2013;33(7):1679-89.
92. B R, XL Z, M B, G VG, EP B, MP L. Caveolin-1 regulates transforming growth factor (TGF)-beta/SMAD signaling through an interaction with the TGF-beta type I receptor. J Biol Chem. 2001;276(9):6727-38.
93. K H, X Y, N L, et al. Internalization of the TGF-β type I receptor into caveolin-1 and EEA1 double-positive early endosomes. Cell Res. 2015;25 (6):738-52.
94. F DG, MP L, SA J. Caveolin-1, transforming growth factor-beta receptor internalization, and the pathogenesis of systemic sclerosis. Curr Opin Rheumatol. 2008;20(6):713-9.
95. SK M, J L, R S, J Z, M L, CJ LS. Caveolin-1 modulates TGF-β1 signaling in cardiac remodeling. Matrix Biol. 2011;30(5-6):318-29.
96. X H, L P, H P, et al. Loss of caveolin-1 promotes endothelial-mesenchymal transition during sepsis: a membrane proteomic study. Int J Mol Med. 2013;32(3):585-92.
97. Z L, PJ W, BS B, MP L, SA J. Caveolin-1 deficiency induces spontaneous endothelial-to-mesenchymal transition in murine pulmonary endothelial cells in vitro. Am J Pathol. 2013; 182(2):325-31.
98. KMRM B, KA D. Endothelin-1 in Health and Disease. Int J Mol Sci. 2023;24(14):doi: 10.3390/ ijms241411295.
99. P C, P DB, P R, et al. The Endothelial-mesenchymal Transition in Systemic Sclerosis Is Induced by Endothelin-1 and Transforming Growth Factor-β and May Be Blocked by Macitentan, a Dual Endothelin-1 Receptor Antagonist. J Rheumatol. 2015;42(10):1808-16.
100. S S, S P, C P, et al. Dual endothelin receptor antagonists contrast the effects induced by endothelin-1 on cultured human microvascular endothelial cells. Clin Exp Rheumatol. 2017;35 (3):484-493.
101. PJ W, Z L, FA M, SA J. Stimulation of Transforming Growth Factor-β1-Induced Endothelial-To-Mesenchymal Transition and Tissue Fibrosis by Endothelin-1 (ET-1): A Novel Profibrotic Effect of ET-1. PLoS One. 2016;11(9):e0161988.
102. ML B, C L, NS R, et al. Activated Endothelial TGFβ1 Signaling Promotes Venous Thrombus Nonresolution in Mice Via Endothelin-1: Potential Role for Chronic Thromboembolic Pulmonary Hypertension. Circ Res. 2020;126(2):162-181.
103. W Z, L W, J Y, et al. Endothelial cell-derived MMP19 promotes pulmonary fibrosis by inducing E(nd)MT and monocyte infiltration. Cell Commun Signal. 2023;21(1):56.
104. H H, J H, S Z, B Z, W L, K S. Tumor necrosis factor-α stimulation endothelial-to-mesenchymal transition during cardiac fibrosis via endothelin-1 signaling. J Biochem Mol Toxicol. 2023;37(9):e23411.
105. SJ B. Notch signalling: a simple pathway becomes complex. Nat Rev Mol Cell Biol. 2006; 7(9):678-89.
106. R K, MX I. The canonical Notch signaling pathway: unfolding the activation mechanism. Cell. 2009;137(2):216-33.
107. JJ M, ML I. NOTCH regulation of the endothelial cell phenotype. Curr Opin Hematol. 2018;25(3):212-218.
108. T W, X X, X T, et al. Serelaxin alleviates cardiac fibrosis through inhibiting endothelial-to-mesenchymal transition via RXFP1. Theranostics. 2020;10(9): 3905-3924.
109. J Z, J P, S K, et al. Sox9 and Rbpj differentially regulate endothelial to mesenchymal transition and wound scarring in murine endovascular progenitors. Nat Commun. 2021;12(1):2564.
110. R Y, F Y, Y H, et al. Hepatocyte Growth Factor Attenuates the Development of TGF-β1- Induced EndMT through Down-regulating the Notch Signaling. Endocr Metab Immune Disord Drug Targets. 2020;20(5):781-787.
111. Y H, XX Q, MW L, W S. Morin, a matrix metalloproteinase 9 inhibitor, attenuates endothelial-to-mesenchymal transition in atherosclerosis by downregulating Notch-1 signaling. J Integr Med. 2024;22(6):683-695.
112. P D, A B, A M. Interplay between BMP2 and Notch signaling in endothelial-mesenchymal transition: implications for cardiac fibrosis. Stem Cell Investig. 2023;10:18.
113. R M, L O, P V. Human endothelial cell cultures: phenotypic modulation by leukocyte interleukins. J Cell Physiol. 1985;122(3):424-34.
114. L P, N M, CA R, et al. Endothelial-to-mesenchymal transition: Cytokine-mediated pathways that determine endothelial fibrosis under inflammatory conditions. Cytokine Growth Factor Rev. 2017;33:41-54.
115. M M, JR M, N H, B VDS, G K, MC H. IL-1β and TGFβ2 synergistically induce endothelial to mesenchymal transition in an NFκB-dependent manner. Immunobiology. 2013;218(4):443-54.
116. LI R, DN Z, GS H, MA K. Interleukin-1 induces major phenotypic changes in human skin microvascular endothelial cells. J Cell Physiol. 1997;173(1):84-92.
117. OK H, SS L, SJ Y, et al. Gemigliptin Inhibits Interleukin-1β-Induced Endothelial-Mesenchymal Transition via Canonical-Bone Morphogenetic Protein Pathway. Endocrinol Metab (Seoul). 2020; 35(2):384-395.
118. CC L, CS P, CY W, SW L, LD H, CM Y. Tumor necrosis factor-alpha induces VCAM-1-mediated inflammation via c-Src-dependent transactivation of EGF receptors in human cardiac fibroblasts. J Biomed Sci. 2015;22(1):53.
119. V C, L Z, M K. Inflammatory cytokines induce the transformation of human dermal microvascular endothelial cells into myofibroblasts: a potential role in skin fibrogenesis. J Cutan Pathol. 2007; 34(2):146-53.
120. M A, P S, J G, et al. TNF-α induces endothelial-mesenchymal transition promoting stromal development of pancreatic adenocarcinoma. Cell Death Dis. 2021;12(7):649.
121. GJ M, EJ F, JT B. Inflammatory cytokines promote mesenchymal transformation in embryonic and adult valve endothelial cells. Arterioscler Thromb Vasc Biol. 2013;33(1):121-30.
122. Y T, SM L, Z D, M K, K K, D K. Endothelial autophagy deficiency induces IL6 - dependent endothelial mesenchymal transition and organ fibrosis. Autophagy. 2020;16(10):1905-1914.
123. K T, M Y, T M, et al. IL-13 enhances mesenchymal transition of pulmonary artery endothelial cells via down-regulation of miR-424/503 in vitro. Cell Signal. 2018;42:270-280.
124. HZ J, L C, M R, et al. CXCL8 Promotes Endothelial-to-Mesenchymal Transition of Endothelial Cells and Protects Cells from Erastin-Induced Ferroptosis via CXCR2-Mediated Activation of the NF-κB Signaling Pathway. Pharmaceuticals (Basel). 2023;16(9):doi: 10.3390/ph16091210.
125. J F, K L, F X, L H, Y W. IL-35 ameliorates lipopolysaccharide-induced endothelial dysfunction by inhibiting endothelial-to-mesenchymal transition. Int Immunopharmacol. 2024;129:111567.
126. I C, S L, L S, M T. Interferon-γ promotes vascular remodeling in human microvascular endothelial cells by upregulating endothelin (ET)-1 and transforming growth factor (TGF) β2. J Cell Physiol. 2013;228(8):1774-83.
127. T W, B L, J H, et al. IFN-γ-mediated inhibition of JAK/STAT signaling via nano-scutellarin treatment is an efficient strategy for ameliorating liver fibrosis. J Transl Med. 2025;23(1):195.
128. J C, R Y, Q T, et al. METTL3-mediated m6A modification of TNFAIP3 promotes endothelial to mesenchymal transition and atherosclerosis via the NF-κB/SNAIL signaling pathway. J Lipid Res. 2025;66(12):100931.
129. Z G, X Z, Q H, et al. Macrophage polarization induces endothelium-to-myofibroblast transition in chronic allograft dysfunction. Ren Fail. 2023;45 (1):2220418.
130. M M, A S, R K, et al. CD163(+) Macrophages Induce Endothelial-to-Mesenchymal Transition in Atheroma. Circ Res. 2024;135(2):e4-e23.
131. E P, N R, M G, et al. Neutrophil Extracellular Traps Drive Endothelial-to-Mesenchymal Transition. Arterioscler Thromb Vasc Biol. 2017;37(7):1371-1379.
132. FC O, R S, M A, et al. Pharmacological blocking of neutrophil extracellular traps attenuates immunothrombosis and neuroinflammation in cerebral cavernous malformation. Nat Cardiovasc Res. 2024;3(12):1549-1567.
133. LW H, S J, JC H, et al. A Phase 1a Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of RO7303509, an Anti-TGFβ3 Antibody, in Healthy Volunteers. Rheumatol Ther. 2024;11(3):755-771.
134. N P, M W, CR O, et al. Identification and development of a subtype-selective allosteric AKT inhibitor suitable for clinical development. Sci Rep. 2022;12(1):15715.
135. A S, KJ O, DJ R. Epigenetic drugs in cancer therapy. Cancer Metastasis Rev. 2025;44(1):37.
136. MA MN, M M, A Z, S C. Versatile lactate signaling via HCAR1: a multifaceted GPCR involved in many biological processes. Am J Physiol Cell Physiol. 2023;325(6):C1502-C1515.
137. T K, L F. Exploring monocarboxylate transporter inhibition for cancer treatment. Explor Target Antitumor Ther. 2024;5(1):135-169.
2. S P, SA J. Endothelial to Mesenchymal Transition: Role in Physiology and in the Pathogenesis of Human Diseases. Physiol Rev. 2019;99(2):1281-1324.
3. X L, J G, PA D, H Y. Endothelial-to-mesenchymal transition: Pathogenesis and therapeutic targets for chronic pulmonary and vascular diseases. Biochem Pharmacol. 2019;168:100-107.
4. SA J, S P. Endothelial to mesenchymal transition (EndoMT) in the pathogenesis of Systemic Sclerosis-associated pulmonary fibrosis and pulmonary arterial hypertension. Myth or reality?. Matrix Biol. 2016;51:26-36.
5. I M, A B, R C, et al. Oxidative stress mediates the conversion of endothelial cells into myofibroblasts via a TGF-β1 and TGF-β2-dependent pathway. Lab Invest. 2014;94(10):1068-82.
6. Y L, Y X, Y S, et al. Exosomes derived from adipose tissue-derived stem cells alleviated H(2)O(2)-induced oxidative stress and endothelial-to-mesenchymal transition in human umbilical vein endothelial cells by inhibition of the mir-486-3p/Sirt6/Smad signaling pathway. Cell Biol Toxicol. 2024;40(1):39.
7. GR D, CG S. Endothelial NADPH oxidases: which NOX to target in vascular disease?. Trends Endocrinol Metab. 2014;25(9):452-63.
8. THG P, AM P, R G, et al. NADPH Oxidase-Derived Reactive Oxygen Species Generation Drives Endothelial-to-Mesenchymal Transition in Human Pulmonary Endothelial Cells Exposed to Sera From Patients With Idiopathic Pulmonary Fibrosis. J Cardiovasc Pharmacol. 2026;87(1):28-39.
9. X C, X X, T D, Z L, L D, H Z. Trimetazidine Reduces Cardiac Fibrosis in Rats by Inhibiting NOX2-Mediated Endothelial-to-Mesenchymal Transition. Drug Des Devel Ther. 2022;16:2517-2527.
10. S P, A M, SA J. Increased expression of NAPDH oxidase 4 in systemic sclerosis dermal fibroblasts: regulation by transforming growth factor β. Arthritis Rheumatol. 2015;67(10):2749-58.
11. F G, Y Z, B Z, et al. SESN1 attenuates the Ox‑LDL‑induced inflammation, apoptosis and endothelial‑mesenchymal transition of human umbilical vein endothelial cells by regulating AMPK/SIRT1/LOX1 signaling. Mol Med Rep. 2022;25(5):pii: 161. doi: 10.3892/mmr.2022.12678.
12. J X, H K, Y Y, et al. A Metabolic Basis for Endothelial-to-Mesenchymal Transition. Mol Cell. 2018;69(4):689-698.e7.
13. E A, F M, S P, et al. Glycolysis-derived acidic microenvironment as a driver of endothelial dysfunction in systemic sclerosis. Rheumatology (Oxford). 2021;60(10):4508-4519.
14. LJ C, JY L, P N, et al. Single-cell RNA sequencing unveils unique transcriptomic signatures of endothelial cells and role of ENO1 in response to disturbed flow. Proc Natl Acad Sci U S A. 2024;121(5):e2318904121.
15. C L, M L, W W, Y L, Z H, Z X. RNA-seq and ChIP-seq reveal microplastics induce endothelial-mesenchymal transition via HK2-mediated histone lactylation in pulmonary hypertension. Vascul Pharmacol. 2026;162:107571.
16. D Z, Z T, H H, et al. Metabolic regulation of gene expression by histone lactylation. Nature. 2019;574(7779):575-580.
17. X H, W C, M Y, M L, X L, S O. IGFBP5 promotes EndoMT and renal fibrosis through H3K18 lactylation in diabetic nephropathy. Cell Mol Life Sci. 2025;82(1):215.
18. SH C, ZY H, JK N, et al. A Hypoxia-Induced Vascular Endothelial-to-Mesenchymal Transition in Development of Radiation-Induced Pulmonary Fibrosis. Clin Cancer Res. 2015;21(16):3716-26.
19. M D, J M, L B, BL C, A V. Differential effect of hypoxia on early endothelial-mesenchymal transition response to transforming growth beta isoforms 1 and 2. Microvasc Res. 2016;108:48-63.
20. X X, X T, B T, E S, M Z, EM Z. Snail Is a Direct Target of Hypoxia-inducible Factor 1α (HIF1α) in Hypoxia-induced Endothelial to Mesenchymal Transition of Human Coronary Endothelial Cells. J Biol Chem. 2015;290(27):16653-64.
21. T S, EJ C, MH T, et al. Isolation and characterization of endothelial-to-mesenchymal transition cells in pulmonary arterial hypertension. Am J Physiol Lung Cell Mol Physiol. 2018; 314(1):L118-L126.
22. S S, M Z, Z Y, et al. The role of PDGF-B/TGF-β1/neprilysin network in regulating endothelial-to-mesenchymal transition in pulmonary artery remodeling. Cell Signal. 2016;28(10):1489-501.
23. H T, A B, KM M, et al. Endothelial HIF-2α contributes to severe pulmonary hypertension due to endothelial-to-mesenchymal transition. Am J Physiol Lung Cell Mol Physiol. 2018;314(2):L256-L275.
24. Y Z, K Y, Z Z, et al. The HIF2α-dependent upregulation of SETDB1 facilitates hypoxia-induced functional and phenotypical changes of pulmonary microvascular endothelial cells. Am J Physiol Cell Physiol. 2025;328(1):C40-C55.
25. Y L, J Z, B L, et al. RUNX3 modulates hypoxia-induced endothelial-to-mesenchymal transition of human cardiac microvascular endothelial cells. Int J Mol Med. 2017;40(1):65-74.
26. I S, M P, J H, R S, G E. Endothelial Mesenchymal Transition in Hypoxic Microvascular Endothelial Cells and Paracrine Induction of Cardiomyocyte Apoptosis Are Mediated via TGFβ₁/SMAD Signaling. Int J Mol Sci. 2017;18(11):doi: 10.3390/ ijms18112290.
27. H Z, Y L, L Y, et al. Bone morphogenetic protein-7 inhibits endothelial-mesenchymal transition in pulmonary artery endothelial cell under hypoxia. J Cell Physiol. 2018;233(5):4077-4090.
28. L L, J C, L S, Y X. RhoJ promotes hypoxia induced endothelial-to-mesenchymal transition by activating WDR5 expression. J Cell Biochem. 2018;119(4):3384-3393.
29. R T, Q L, L L, et al. Angiotensin II mediates the high-glucose-induced endothelial-to-mesenchymal transition in human aortic endothelial cells. Cardiovasc Diabetol. 2010;9:31.
30. RN T, LL L, JD Z, et al. Effects of angiotensin II receptor blocker on myocardial endothelial-to-mesenchymal transition in diabetic rats. Int J Cardiol. 2013;162(2):92-9.
31. Y C, B F, S C, Y C, S C. Mechanisms of endothelial to mesenchymal transition in the retina in diabetes. Invest Ophthalmol Vis Sci. 2014; 55(11):7321-31.
32. Y C, Q Y, Y Z, J K, P L, J H. The role of miR-328 in high glucose-induced endothelial-to-mesenchymal transition in human umbilical vein endothelial cells. Life Sci. 2018;207:110-116.
33. CH Y, Suriguga, M G, et al. High glucose induced endothelial to mesenchymal transition in human umbilical vein endothelial cell. Exp Mol Pathol. 2017;102(3):377-383.
34. H P, Y L, C W, et al. ROCK1 Induces Endothelial -to-Mesenchymal Transition in Glomeruli to Aggravate Albuminuria in Diabetic Nephropathy. Sci Rep. 2016;6:20304.
35. J Z, S C, H X, et al. S1PR2/Wnt3a/RhoA/ ROCK1/β-catenin signaling pathway promotes diabetic nephropathy by inducting endothelial mesenchymal transition and impairing endothelial barrier function. Life Sci. 2023;328:121853.
36. C F, Y L, J C, et al. Apelin Alleviated Endothelial-To-Mesenchymal Transition via Increasing BKCa in Diabetic Nephropathy. FASEB J. 2025;39(12):e70747.
37. Z M, W S, L Y, et al. Bach1 modulates AKT3 transcription to participate in hyperglycaemia-mediated EndMT in vascular endothelial cells. Clin Exp Pharmacol Physiol. 2023;50(6):443-452.
38. Y T, Z B, S G, B Y, W H. STAT5A modulated EndMT via upregulation of ELTD1 expression in diabetic nephropathy. Clin Exp Pharmacol Physiol. 2022;49(6):686-695.
39. L L, M Z, Q W, Z S, X C, C M. Sirt7/HIC1 complex participates in hyperglycaemia-mediated EndMT via modulation of SDC1 expression in diabetic kidney disease and metabolic memory. J Cell Mol Med. 2024;28(9):e18336.
40. M W, Y H, X W, et al. SirT7-mediated transcription of fascin in hyperglycemic glomerular endothelial cells contributes to EndMT in diabetic nephropathy. Acta Biochim Biophys Sin (Shanghai). 2024;56(4):586-596.
41. X L, L L, W H, et al. The SETD8/ELK1/bach1 complex regulates hyperglycaemia-mediated EndMT in diabetic nephropathy. J Transl Med. 2022;20(1):147.
42. SM W, JN T. Adaptation of the endothelium to fluid flow: in vitro analyses of gene expression and in vivo implications. Vasc Med. 2004;9(1):35-45.
43. Y F, D W, KG B. Mechanosensing and Mechanoregulation of Endothelial Cell Functions. Compr Physiol. 2019;9(2):873-904.
44. BJ B, A D, E E, A L. Shear stress and the endothelium. Kidney Int Suppl. 1998;67:S100-8.
45. KS C, AI G. The role of shear stress in the pathogenesis of atherosclerosis. Lab Invest. 2005; 85(1):9-23.
46. GJ M, CM F, Q C, JT B. Effects of shear stress pattern and magnitude on mesenchymal transformation and invasion of aortic valve endothelial cells. Biotechnol Bioeng. 2014;111(11):2326-37.
47. MM M, J S, S F, et al. Shear stress induces endothelial-to-mesenchymal transition via the transcription factor Snail. Sci Rep. 2017;7(1):3375.
48. K Z, W L, DD G, et al. Hydrogen sulfide attenuates atherosclerosis induced by low shear stress by sulfhydrylating endothelium NFIL3 to restrain MEST mediated endothelial mesenchymal transformation. Nitric Oxide. 2024;142:47-57.
49. A L, L T, S Z, J T, Z W, D W. Low shear stress-induced endothelial mesenchymal transformation via the down-regulation of TET2. Biochem Biophys Res Commun. 2021;545:20-26.
50. H D, MA S. High Fluid Shear Stress Inhibits Cytokine-Driven Smad2/3 Activation in Vascular Endothelial Cells. J Am Heart Assoc. 2022; 11(14):e025337.
51. T S, JR M, YH C, et al. High Shear Stress Reduces ERG Causing Endothelial-Mesenchymal Transition and Pulmonary Arterial Hypertension. Arterioscler Thromb Vasc Biol. 2025;45(2):218-237.
52. JR M, ES L, M S, et al. Endothelial-to-mesenchymal transition contributes to fibro-proliferative vascular disease and is modulated by fluid shear stress. Cardiovasc Res. 2015;108(3):377-86.
53. K CL, A S, V B, et al. Shear Stress Alterations Activate BMP4/pSMAD5 Signaling and Induce Endothelial Mesenchymal Transition in Varicose Veins. Cells. 2021;10(12):doi: 10.3390/cells10123563.
54. NA O, X H, IP D, et al. Abnormal Flow Conditions Promote Endocardial Fibroelastosis Via Endothelial-to-Mesenchymal Transition, Which Is Responsive to Losartan Treatment. JACC Basic Transl Sci. 2021;6(12):984-999.
55. E K, M P, S C, et al. The interleukin-1 receptor type-1 in disturbed flow-induced endothelial mesenchymal activation. Front Cardiovasc Med. 2023;10:1190460.
56. CL K, V V, BJ S, et al. Oscillatory shear stress modulates Notch-mediated endothelial mesenchymal plasticity in cerebral arteriovenous malformations. Cell Mol Biol Lett. 2023;28(1):22.
57. S A, CL K, BJ S, SR K, S S. Altered venous flow drives endothelial to mesenchymal transition in varicose veins by suppressing PIEZO1-KLF2 signaling. Cell Mol Life Sci. 2025;82(1):345.
58. Collaborators G2RF. Global burden and strength of evidence for 88 risk factors in 204 countries and 811 subnational locations, 1990-2021: a systematic analysis for the Global Burden of Disease Study 2021. Lancet. 2024;403(10440): 2162-2203.
59. CJ W, RJ S, KC P, et al. Exposure to Ambient Particulate Matter Is Associated With Accelerated Functional Decline in Idiopathic Pulmonary Fibrosis. Chest. 2018;153(5):1221-1228.
60. B L, Y H, Y Y, X W, G L, W J. Atmospheric fine particulate matter (PM(2.5)) induces pulmonary fibrosis by regulating different cell fates via autophagy. Sci Total Environ. 2024;923:171396.
61. K M, C L, J X, et al. LncRNA Gm16410 regulates PM(2.5)-induced lung Endothelial-Mesenchymal Transition via the TGF-β1/Smad3/p-Smad3 pathway. Ecotoxicol Environ Saf. 2020;205:111327.
62. Q S, M W, L L, et al. PM(2.5) Induce Endothelial-Mesenchymal Transition and Cardiac Fibrosis via the NCOA4-Mediated Ferritinophagy. Adv Sci (Weinh). 2025;12(45):e07536.
63. JH P, JY C, GY K, M K, SH P, YH K. Endothelial BACE1, regulating the endothelial-to-mesenchymal transition (EndMT) induced by particulate matter (PM), is associated with cerebrovascular disease: Involvement of endothelial BACE1 in BBB disruption caused by diabetes. Free Radic Biol Med. 2026;243:96-110.
64. CH H, A M. Role of Smads in TGFβ signaling. Cell Tissue Res. 2012;347(1):21-36.
65. J M, G S, MJ G, P TD. TGF-β-Induced Endothelial to Mesenchymal Transition in Disease and Tissue Engineering. Front Cell Dev Biol. 2020;8:260.
66. H S, A V, PR S. Isoform-specific effects of transforming growth factor β on endothelial-to-mesenchymal transition. J Cell Physiol. 2018; 233(11):8418-8428.
67. M M, R D, K M. TGF-β and the TGF-β Family: Context-Dependent Roles in Cell and Tissue Physiology. Cold Spring Harb Perspect Biol. 2016;8(5):doi: 10.1101/cshperspect.a021873.
68. BC C, J N, J M, et al. TGF-β signaling mediates endothelial-to-mesenchymal transition (EndMT) during vein graft remodeling. Sci Transl Med. 2014;6(227):227ra34.
69. J M, G VDZ, MAFV G, et al. TGF-β-Induced Endothelial to Mesenchymal Transition Is Determined by a Balance Between SNAIL and ID Factors. Front Cell Dev Biol. 2021;9:616610.
70. D M, S P, R K. Transforming growth factor-β2 promotes Snail-mediated endothelial-mesenchymal transition through convergence of Smad-dependent and Smad-independent signalling. Biochem J. 2011;437(3):515-20.
71. L C, H S, Z T, et al. DUSP22 Ameliorates Endothelial-to-Mesenchymal Transition in HUVECs through Smad2/3 and MAPK Signaling Pathways. Cardiovasc Ther. 2024;2024:5583961.
72. R K, W C. Endothelial-to-Mesenchymal Transition in Health and Disease: Molecular Insights and Therapeutic Implications. Int J Mol Sci. 2025;26(23):doi: 10.3390/ijms262311724.
73. T F, M I, T I. A ROCK inhibitor suppresses the transforming growth factor-beta-2-induced endothelial-mesenchymal transition in Schlemm's canal endothelial cells. Sci Rep. 2023;13(1):9655.
74. Z L, SA J. Protein kinase Cδ and c-Abl kinase are required for transforming growth factor β induction of endothelial-mesenchymal transition in vitro. Arthritis Rheum. 2011;63(8):2473-83.
75. R N, H C. Wnt/β-Catenin Signaling, Disease, and Emerging Therapeutic Modalities. Cell. 2017; 169(6):985-999.
76. O A, M R, S R, N A, I F, AK H. Experimental myocardial infarction triggers canonical Wnt signaling and endothelial-to-mesenchymal transition. Dis Model Mech. 2011;4(4):469-83.
77. L L, L C, J Z, et al. C3a and C5a receptor antagonists ameliorate endothelial-myofibroblast transition via the Wnt/β-catenin signaling pathway in diabetic kidney disease. Metabolism. 2015; 64(5):597-610.
78. AV G, MS E, S D, et al. TGF-β1, pSmad-2/3, Smad-7, and β-Catenin Are Augmented in the Pulmonary Arteries from Patients with Idiopathic Pulmonary Fibrosis (IPF): Role in Driving Endothelial-to-Mesenchymal Transition (EndMT). J Clin Med. 2024;13(4):doi: 10.3390/jcm13041160.
79. X S, J F, F Y, et al. Diffuse Large B-Cell Lymphoma Promotes Endothelial-to-Mesenchymal Transition via WNT10A/Beta-Catenin/Snail Signaling. Front Oncol. 2022;12:871788.
80. M S, Y F, J W, Y Y, F Y. CXCR7 Inhibits Fibrosis via Wnt/β-Catenin Pathways during the Process of Angiogenesis in Human Umbilical Vein Endothelial Cells. Biomed Res Int. 2020;2020:1216926.
81. Z W, Z W, L G, et al. miR-222 inhibits cardiac fibrosis in diabetic mice heart via regulating Wnt/β-catenin-mediated endothelium to mesenchymal transition. J Cell Physiol. 2020;235(3):2149-2160.
82. AR K, JL K, Y K, S K, SC O, JK P. A novel RIP1-mediated canonical WNT signaling pathway that promotes colorectal cancer metastasis via β -catenin stabilization-induced EMT. Cancer Gene Ther. 2023;30(10):1403-1413.
83. SH W, JS C, JR H, et al. Tumour cell-derived WNT5B modulates in vitro lymphangiogenesis via induction of partial endothelial-mesenchymal transition of lymphatic endothelial cells. Oncogene. 2017; 36(11):1503-1515.
84. ZY Z, C Z, XY Y, HB L, LL W, L L. Knockdown of CD146 promotes endothelial-to-mesenchymal transition via Wnt/β-catenin pathway. PLoS One. 2022;17(8):e0273542.
85. M L, H D, NL J, et al. Dickkopf-3 in aberrant endothelial secretome triggers renal fibroblast activation and endothelial-mesenchymal transition. Nephrol Dial Transplant. 2019;34(1):49-62.
86. Y W, L S, X J, M Y, W X. miR-29 inhibits endothelial-to-mesenchymal transition in pulmonary hypertension of the newborn by regulating LRP6. FASEB J. 2025;39(7):e70502.
87. Z A, Y N, LSA P, et al. Wnt Site Signaling Inhibitor Secreted Frizzled-Related Protein 3 Protects Mitral Valve Endothelium From Myocardial Infarction-Induced Endothelial-to-Mesenchymal Transition. J Am Heart Assoc. 2022;11(7):e023695.
88. Y F, Z C, Z X, et al. Osteoglycin silencing exerts inhibitory effects on myocardial fibrosis and epithelial/endothelial-mesenchymal transformation in a mouse model of myocarditis. Biofactors. 2020; 46(6):1018-1030.
89. W W, S C, Z X, et al. von Willebrand Factor Deficiency Inhibits Endothelial-to-Mesenchymal Transition to Attenuate Pulmonary Fibrosis. Am J Respir Cell Mol Biol. 2025;73(6):906-919.
90. EJ D, LY C, KS A, et al. Inflammation and DKK1-induced AKT activation contribute to endothelial dysfunction following NR2F2 loss. Am J Physiol Lung Cell Mol Physiol. 2023;324(6):L783-L798.
91. SL C, JS S, A B, K K, DA T. Dkk1 and MSX2-Wnt7b signaling reciprocally regulate the endothelial-mesenchymal transition in aortic endothelial cells. Arterioscler Thromb Vasc Biol. 2013;33(7):1679-89.
92. B R, XL Z, M B, G VG, EP B, MP L. Caveolin-1 regulates transforming growth factor (TGF)-beta/SMAD signaling through an interaction with the TGF-beta type I receptor. J Biol Chem. 2001;276(9):6727-38.
93. K H, X Y, N L, et al. Internalization of the TGF-β type I receptor into caveolin-1 and EEA1 double-positive early endosomes. Cell Res. 2015;25 (6):738-52.
94. F DG, MP L, SA J. Caveolin-1, transforming growth factor-beta receptor internalization, and the pathogenesis of systemic sclerosis. Curr Opin Rheumatol. 2008;20(6):713-9.
95. SK M, J L, R S, J Z, M L, CJ LS. Caveolin-1 modulates TGF-β1 signaling in cardiac remodeling. Matrix Biol. 2011;30(5-6):318-29.
96. X H, L P, H P, et al. Loss of caveolin-1 promotes endothelial-mesenchymal transition during sepsis: a membrane proteomic study. Int J Mol Med. 2013;32(3):585-92.
97. Z L, PJ W, BS B, MP L, SA J. Caveolin-1 deficiency induces spontaneous endothelial-to-mesenchymal transition in murine pulmonary endothelial cells in vitro. Am J Pathol. 2013; 182(2):325-31.
98. KMRM B, KA D. Endothelin-1 in Health and Disease. Int J Mol Sci. 2023;24(14):doi: 10.3390/ ijms241411295.
99. P C, P DB, P R, et al. The Endothelial-mesenchymal Transition in Systemic Sclerosis Is Induced by Endothelin-1 and Transforming Growth Factor-β and May Be Blocked by Macitentan, a Dual Endothelin-1 Receptor Antagonist. J Rheumatol. 2015;42(10):1808-16.
100. S S, S P, C P, et al. Dual endothelin receptor antagonists contrast the effects induced by endothelin-1 on cultured human microvascular endothelial cells. Clin Exp Rheumatol. 2017;35 (3):484-493.
101. PJ W, Z L, FA M, SA J. Stimulation of Transforming Growth Factor-β1-Induced Endothelial-To-Mesenchymal Transition and Tissue Fibrosis by Endothelin-1 (ET-1): A Novel Profibrotic Effect of ET-1. PLoS One. 2016;11(9):e0161988.
102. ML B, C L, NS R, et al. Activated Endothelial TGFβ1 Signaling Promotes Venous Thrombus Nonresolution in Mice Via Endothelin-1: Potential Role for Chronic Thromboembolic Pulmonary Hypertension. Circ Res. 2020;126(2):162-181.
103. W Z, L W, J Y, et al. Endothelial cell-derived MMP19 promotes pulmonary fibrosis by inducing E(nd)MT and monocyte infiltration. Cell Commun Signal. 2023;21(1):56.
104. H H, J H, S Z, B Z, W L, K S. Tumor necrosis factor-α stimulation endothelial-to-mesenchymal transition during cardiac fibrosis via endothelin-1 signaling. J Biochem Mol Toxicol. 2023;37(9):e23411.
105. SJ B. Notch signalling: a simple pathway becomes complex. Nat Rev Mol Cell Biol. 2006; 7(9):678-89.
106. R K, MX I. The canonical Notch signaling pathway: unfolding the activation mechanism. Cell. 2009;137(2):216-33.
107. JJ M, ML I. NOTCH regulation of the endothelial cell phenotype. Curr Opin Hematol. 2018;25(3):212-218.
108. T W, X X, X T, et al. Serelaxin alleviates cardiac fibrosis through inhibiting endothelial-to-mesenchymal transition via RXFP1. Theranostics. 2020;10(9): 3905-3924.
109. J Z, J P, S K, et al. Sox9 and Rbpj differentially regulate endothelial to mesenchymal transition and wound scarring in murine endovascular progenitors. Nat Commun. 2021;12(1):2564.
110. R Y, F Y, Y H, et al. Hepatocyte Growth Factor Attenuates the Development of TGF-β1- Induced EndMT through Down-regulating the Notch Signaling. Endocr Metab Immune Disord Drug Targets. 2020;20(5):781-787.
111. Y H, XX Q, MW L, W S. Morin, a matrix metalloproteinase 9 inhibitor, attenuates endothelial-to-mesenchymal transition in atherosclerosis by downregulating Notch-1 signaling. J Integr Med. 2024;22(6):683-695.
112. P D, A B, A M. Interplay between BMP2 and Notch signaling in endothelial-mesenchymal transition: implications for cardiac fibrosis. Stem Cell Investig. 2023;10:18.
113. R M, L O, P V. Human endothelial cell cultures: phenotypic modulation by leukocyte interleukins. J Cell Physiol. 1985;122(3):424-34.
114. L P, N M, CA R, et al. Endothelial-to-mesenchymal transition: Cytokine-mediated pathways that determine endothelial fibrosis under inflammatory conditions. Cytokine Growth Factor Rev. 2017;33:41-54.
115. M M, JR M, N H, B VDS, G K, MC H. IL-1β and TGFβ2 synergistically induce endothelial to mesenchymal transition in an NFκB-dependent manner. Immunobiology. 2013;218(4):443-54.
116. LI R, DN Z, GS H, MA K. Interleukin-1 induces major phenotypic changes in human skin microvascular endothelial cells. J Cell Physiol. 1997;173(1):84-92.
117. OK H, SS L, SJ Y, et al. Gemigliptin Inhibits Interleukin-1β-Induced Endothelial-Mesenchymal Transition via Canonical-Bone Morphogenetic Protein Pathway. Endocrinol Metab (Seoul). 2020; 35(2):384-395.
118. CC L, CS P, CY W, SW L, LD H, CM Y. Tumor necrosis factor-alpha induces VCAM-1-mediated inflammation via c-Src-dependent transactivation of EGF receptors in human cardiac fibroblasts. J Biomed Sci. 2015;22(1):53.
119. V C, L Z, M K. Inflammatory cytokines induce the transformation of human dermal microvascular endothelial cells into myofibroblasts: a potential role in skin fibrogenesis. J Cutan Pathol. 2007; 34(2):146-53.
120. M A, P S, J G, et al. TNF-α induces endothelial-mesenchymal transition promoting stromal development of pancreatic adenocarcinoma. Cell Death Dis. 2021;12(7):649.
121. GJ M, EJ F, JT B. Inflammatory cytokines promote mesenchymal transformation in embryonic and adult valve endothelial cells. Arterioscler Thromb Vasc Biol. 2013;33(1):121-30.
122. Y T, SM L, Z D, M K, K K, D K. Endothelial autophagy deficiency induces IL6 - dependent endothelial mesenchymal transition and organ fibrosis. Autophagy. 2020;16(10):1905-1914.
123. K T, M Y, T M, et al. IL-13 enhances mesenchymal transition of pulmonary artery endothelial cells via down-regulation of miR-424/503 in vitro. Cell Signal. 2018;42:270-280.
124. HZ J, L C, M R, et al. CXCL8 Promotes Endothelial-to-Mesenchymal Transition of Endothelial Cells and Protects Cells from Erastin-Induced Ferroptosis via CXCR2-Mediated Activation of the NF-κB Signaling Pathway. Pharmaceuticals (Basel). 2023;16(9):doi: 10.3390/ph16091210.
125. J F, K L, F X, L H, Y W. IL-35 ameliorates lipopolysaccharide-induced endothelial dysfunction by inhibiting endothelial-to-mesenchymal transition. Int Immunopharmacol. 2024;129:111567.
126. I C, S L, L S, M T. Interferon-γ promotes vascular remodeling in human microvascular endothelial cells by upregulating endothelin (ET)-1 and transforming growth factor (TGF) β2. J Cell Physiol. 2013;228(8):1774-83.
127. T W, B L, J H, et al. IFN-γ-mediated inhibition of JAK/STAT signaling via nano-scutellarin treatment is an efficient strategy for ameliorating liver fibrosis. J Transl Med. 2025;23(1):195.
128. J C, R Y, Q T, et al. METTL3-mediated m6A modification of TNFAIP3 promotes endothelial to mesenchymal transition and atherosclerosis via the NF-κB/SNAIL signaling pathway. J Lipid Res. 2025;66(12):100931.
129. Z G, X Z, Q H, et al. Macrophage polarization induces endothelium-to-myofibroblast transition in chronic allograft dysfunction. Ren Fail. 2023;45 (1):2220418.
130. M M, A S, R K, et al. CD163(+) Macrophages Induce Endothelial-to-Mesenchymal Transition in Atheroma. Circ Res. 2024;135(2):e4-e23.
131. E P, N R, M G, et al. Neutrophil Extracellular Traps Drive Endothelial-to-Mesenchymal Transition. Arterioscler Thromb Vasc Biol. 2017;37(7):1371-1379.
132. FC O, R S, M A, et al. Pharmacological blocking of neutrophil extracellular traps attenuates immunothrombosis and neuroinflammation in cerebral cavernous malformation. Nat Cardiovasc Res. 2024;3(12):1549-1567.
133. LW H, S J, JC H, et al. A Phase 1a Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of RO7303509, an Anti-TGFβ3 Antibody, in Healthy Volunteers. Rheumatol Ther. 2024;11(3):755-771.
134. N P, M W, CR O, et al. Identification and development of a subtype-selective allosteric AKT inhibitor suitable for clinical development. Sci Rep. 2022;12(1):15715.
135. A S, KJ O, DJ R. Epigenetic drugs in cancer therapy. Cancer Metastasis Rev. 2025;44(1):37.
136. MA MN, M M, A Z, S C. Versatile lactate signaling via HCAR1: a multifaceted GPCR involved in many biological processes. Am J Physiol Cell Physiol. 2023;325(6):C1502-C1515.
137. T K, L F. Exploring monocarboxylate transporter inhibition for cancer treatment. Explor Target Antitumor Ther. 2024;5(1):135-169.