Alveolar epithelial cell dysfunction and epithelial-mesenchymal transition in pulmonary fibrosis pathogenesis
Pulmonary fibrosis (PF) is a progressive and lethal interstitial lung disease characterized by aberrant scar formation and destruction of alveolar architecture. Dysfunctional alveolar epithelial cells (AECs) play a central role in initiating PF, where chronic injury triggers apoptosis and disrupts e...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2025-04-01
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| Series: | Frontiers in Molecular Biosciences |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmolb.2025.1564176/full |
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| author | Caopei Zheng Caopei Zheng Ling Zhang Ling Zhang Yuqing Sun Yuqing Sun Yingmin Ma Yulin Zhang Yulin Zhang Yulin Zhang |
| author_facet | Caopei Zheng Caopei Zheng Ling Zhang Ling Zhang Yuqing Sun Yuqing Sun Yingmin Ma Yulin Zhang Yulin Zhang Yulin Zhang |
| author_sort | Caopei Zheng |
| collection | DOAJ |
| description | Pulmonary fibrosis (PF) is a progressive and lethal interstitial lung disease characterized by aberrant scar formation and destruction of alveolar architecture. Dysfunctional alveolar epithelial cells (AECs) play a central role in initiating PF, where chronic injury triggers apoptosis and disrupts epithelial homeostasis, leading to epithelial-mesenchymal transition (EMT). This dynamic reprogramming process causes AECs to shed epithelial markers and adopt a mesenchymal phenotype, fueling fibroblast activation and pathological extracellular matrix (ECM) deposition. This review systematically explores the multi-layered mechanisms driving AECs dysfunction and EMT, focusing on core signaling axes such as transforming growth factor-β (TGF-β)/Smad, WNT/β-catenin, NF-κB-BRD4, and nuclear factor erythroid 2-related factor 2 (Nrf2), which regulate EMT and fibroblast-ECM interactions. It also highlights emerging regulators, including metabolic reprogramming, exosomal miRNA trafficking, and immune-epithelial interactions. Furthermore, understanding these mechanisms is essential for developing targeted therapeutic strategies to modulate these pathways and halt or reverse fibrosis progression, offering critical insights into potential clinical treatments for PF. |
| format | Article |
| id | doaj-art-bcf20ec7bd6a42a18ceac5702fc45994 |
| institution | DOAJ |
| issn | 2296-889X |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Biosciences |
| spelling | doaj-art-bcf20ec7bd6a42a18ceac5702fc459942025-08-20T03:15:04ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2025-04-011210.3389/fmolb.2025.15641761564176Alveolar epithelial cell dysfunction and epithelial-mesenchymal transition in pulmonary fibrosis pathogenesisCaopei Zheng0Caopei Zheng1Ling Zhang2Ling Zhang3Yuqing Sun4Yuqing Sun5Yingmin Ma6Yulin Zhang7Yulin Zhang8Yulin Zhang9Department of Respiratory and Critical Care Medicine, Beijing Youan Hospital, Capital Medical University, Beijing, ChinaLaboratory for Clinical Medicine, Capital Medical University, Beijing, ChinaDepartment of Respiratory and Critical Care Medicine, Beijing Youan Hospital, Capital Medical University, Beijing, ChinaBeijing Institute of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing, ChinaDepartment of Respiratory and Critical Care Medicine, Beijing Youan Hospital, Capital Medical University, Beijing, ChinaLaboratory for Clinical Medicine, Capital Medical University, Beijing, ChinaDepartment of Respiratory and Critical Care Medicine, Beijing Youan Hospital, Capital Medical University, Beijing, ChinaDepartment of Respiratory and Critical Care Medicine, Beijing Youan Hospital, Capital Medical University, Beijing, ChinaLaboratory for Clinical Medicine, Capital Medical University, Beijing, ChinaBeijing Research Center for Respiratory Infectious Diseases, Beijing, ChinaPulmonary fibrosis (PF) is a progressive and lethal interstitial lung disease characterized by aberrant scar formation and destruction of alveolar architecture. Dysfunctional alveolar epithelial cells (AECs) play a central role in initiating PF, where chronic injury triggers apoptosis and disrupts epithelial homeostasis, leading to epithelial-mesenchymal transition (EMT). This dynamic reprogramming process causes AECs to shed epithelial markers and adopt a mesenchymal phenotype, fueling fibroblast activation and pathological extracellular matrix (ECM) deposition. This review systematically explores the multi-layered mechanisms driving AECs dysfunction and EMT, focusing on core signaling axes such as transforming growth factor-β (TGF-β)/Smad, WNT/β-catenin, NF-κB-BRD4, and nuclear factor erythroid 2-related factor 2 (Nrf2), which regulate EMT and fibroblast-ECM interactions. It also highlights emerging regulators, including metabolic reprogramming, exosomal miRNA trafficking, and immune-epithelial interactions. Furthermore, understanding these mechanisms is essential for developing targeted therapeutic strategies to modulate these pathways and halt or reverse fibrosis progression, offering critical insights into potential clinical treatments for PF.https://www.frontiersin.org/articles/10.3389/fmolb.2025.1564176/fullalveolar epithelial cellepithelial-mesenchymal transitionmolecular mechanismssignaling pathwayspulmonary fibrosis |
| spellingShingle | Caopei Zheng Caopei Zheng Ling Zhang Ling Zhang Yuqing Sun Yuqing Sun Yingmin Ma Yulin Zhang Yulin Zhang Yulin Zhang Alveolar epithelial cell dysfunction and epithelial-mesenchymal transition in pulmonary fibrosis pathogenesis Frontiers in Molecular Biosciences alveolar epithelial cell epithelial-mesenchymal transition molecular mechanisms signaling pathways pulmonary fibrosis |
| title | Alveolar epithelial cell dysfunction and epithelial-mesenchymal transition in pulmonary fibrosis pathogenesis |
| title_full | Alveolar epithelial cell dysfunction and epithelial-mesenchymal transition in pulmonary fibrosis pathogenesis |
| title_fullStr | Alveolar epithelial cell dysfunction and epithelial-mesenchymal transition in pulmonary fibrosis pathogenesis |
| title_full_unstemmed | Alveolar epithelial cell dysfunction and epithelial-mesenchymal transition in pulmonary fibrosis pathogenesis |
| title_short | Alveolar epithelial cell dysfunction and epithelial-mesenchymal transition in pulmonary fibrosis pathogenesis |
| title_sort | alveolar epithelial cell dysfunction and epithelial mesenchymal transition in pulmonary fibrosis pathogenesis |
| topic | alveolar epithelial cell epithelial-mesenchymal transition molecular mechanisms signaling pathways pulmonary fibrosis |
| url | https://www.frontiersin.org/articles/10.3389/fmolb.2025.1564176/full |
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