MicroRNA-29c Prevents Pulmonary Fibrosis by Regulating Epithelial Cell Renewal and Apoptosis
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Updated: Feb 24, 2026
Refined Murine Model of Idiopathic Pulmonary Fibrosis
Published on: June 17, 2025
Ting Xie1, Jiurong Liang1, Yan Geng1
11 Department of Medicine, Division of Pulmonary and Critical Care Medicine, Women's Guild Lung Institute, Cedars-Sinai Medical Center, Los Angeles, California.
Abstract:
Successful repair and renewal of alveolar epithelial cells (AECs) are critical in prohibiting the accumulation of myofibroblasts in pulmonary fibrogenesis. MicroRNAs (miRNAs) are multifocal regulators involved in lung injury and repair. However, the contribution of miRNAs to AEC2 renewal and apoptosis is incompletely understood. We report that miRNA-29c (miR-29c) expression is lower in AEC2s of individuals with idiopathic pulmonary fibrosis than in healthy lungs. Epithelial cells overexpressing miR-29c show higher proliferative rates and viability. miR-29c protects epithelial cells from apoptosis by targeting forkhead box O3a (Foxo3a). Both overexpression of miR-29c conventionally and AEC2s specifically lead to less fibrosis and better recovery in vivo. Furthermore, deficiency of miR-29c in AEC2s results in higher apoptosis and reduced epithelial renewal. Interestingly, a gene network including a subset of apoptotic genes was coregulated by both Toll-like receptor 4 and miR-29c. Taken together, miR-29c maintains epithelial integrity and promotes recovery from lung injury, thereby attenuating lung fibrosis in mice.
Insights
MicroRNA-29c (miR-29c) is crucial for lung repair. Lower miR-29c levels in idiopathic pulmonary fibrosis lungs impair epithelial cell renewal and promote fibrosis, while higher levels protect against lung injury.
Area of Science:
- Pulmonary Medicine
- Molecular Biology
- Cell Biology
Background:
- Alveolar epithelial cell (AEC) repair is vital for preventing lung fibrosis.
- MicroRNAs (miRNAs) regulate lung injury and repair, but their role in AEC renewal and apoptosis is not fully understood.
Purpose of the Study:
- To investigate the role of microRNA-29c (miR-29c) in alveolar epithelial cell (AEC) renewal and apoptosis.
- To determine the therapeutic potential of miR-29c in mitigating pulmonary fibrosis.
Main Methods:
- Compared miR-29c expression in AECs from idiopathic pulmonary fibrosis (IPF) patients and healthy individuals.
- Overexpressed miR-29c in epithelial cells and AECs to assess effects on proliferation, viability, and apoptosis in vitro and in vivo.
- Investigated the molecular targets of miR-29c, including forkhead box O3a (Foxo3a).
- Analyzed the interplay between miR-29c, Toll-like receptor 4, and apoptotic gene networks.
Main Results:
- miR-29c expression was reduced in AECs from IPF patients.
- Overexpression of miR-29c enhanced epithelial cell proliferation and viability while reducing apoptosis by targeting Foxo3a.
- In vivo studies showed that miR-29c overexpression attenuated lung fibrosis and improved recovery.
- miR-29c deficiency in AECs led to increased apoptosis and impaired epithelial renewal.
- A gene network involving Toll-like receptor 4 and miR-29c was identified, regulating apoptotic genes.
Conclusions:
- miR-29c plays a critical role in maintaining epithelial integrity and promoting lung tissue recovery.
- Restoring miR-29c levels can protect against lung injury and attenuate pulmonary fibrosis.
- miR-29c represents a potential therapeutic target for treating lung fibrosis.
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