Matricellular Regulation of Alveolar Epithelial Cell Plasticity in Neonatal Lung Injury: Insights from CCN5 and Beyond

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Published Nov 1, 2025
DOI: https://doi.org/10.18103/mra.v13i10.6931

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Main Article Content

Najla Fiaturi, MD, PhD, CFD
Department of Medical Education, Tufts University School of Medicine, Boston MA, USA; Graduate Program in Drug Development, Graduate School of Biomedical Sciences, Tufts University School of Medicine, Boston MA, USA
Heber C Nielsen, MD, MSDS
Graduate Program in Genetics, Molecular, and Cell Biology, Tufts Graduate Program in Biomedical Sciences, and Department of Pediatrics, Tufts Medical Center, Boston MA, USA
John Castellot, PhD
Department of Medical Education, Tufts University School of Medicine, Boston MA, USA; Graduate Program in Drug Development, Graduate School of Biomedical Sciences, Tufts University School of Medicine, Boston MA, USA

Abstract

Neonatal lung injury remains a major cause of morbidity among preterm infants and is a leading antecedent of bronchopulmonary dysplasia (BPD), a condition characterized by arrested alveolar development, inflammation, and extracellular matrix (ECM) remodeling. Despite significant advances in neonatal care, the mechanisms governing lung repair and regeneration remain incompletely understood. Recent research highlights the crucial role of matricellular proteins that orchestrate cell signaling, differentiation, and tissue remodeling in modulating epithelial responses to injury. Among these, the CCN (CYR61/CTGF/NOV) family of proteins has emerged as a pivotal regulator of epithelial–mesenchymal communication, with diverse and context-dependent functions in development, fibrosis, and regeneration.


This review examines the distinct role of CCN5 (WISP2) within this family as a modulator of alveolar epithelial cell (AEC) plasticity in neonatal lung injury. We integrate findings from our own work with recent advances in CCN biology to elucidate how CCN5 influences epithelial survival, epithelial–mesenchymal transition (EMT), mitochondrial homeostasis, and intercellular signaling in hyperoxic injury. The review also contrasts CCN5 with other CCN members implicated in fibrotic lung diseases and situates it within broader matricellular signaling networks. By defining how CCN5 mediates epithelial resilience and tissue homeostasis, we propose it as a potential therapeutic target for mitigating BPD and enhancing regenerative outcomes in premature infants.

Keywords: CCN5, alveolar epithelial cells, bronchopulmonary dysplasia, matricellular signaling, neonatal lung injury, extracellular matrix, epithelial plasticity, regenerative biology

Article Details

How to Cite
FIATURI, Najla; NIELSEN, Heber C; CASTELLOT, John. Matricellular Regulation of Alveolar Epithelial Cell Plasticity in Neonatal Lung Injury: Insights from CCN5 and Beyond. Medical Research Archives, [S.l.], v. 13, n. 10, nov. 2025. ISSN 2375-1924. Available at: <https://esmed.org/MRA/mra/article/view/6931>. Date accessed: 06 dec. 2025. doi: https://doi.org/10.18103/mra.v13i10.6931.
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Issue
Vol 13 No 10 (2025): Vol.13, Issue 10, October 2025
Section
Research Articles

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