Academic Journal
Atg5 deficiency alters myofibroblast accumulation and alveolar regeneration in lung fibrosis.
| Τίτλος: | Atg5 deficiency alters myofibroblast accumulation and alveolar regeneration in lung fibrosis. |
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| Συγγραφείς: | Li X; Tianjin Key Laboratory of Lung Regenerative Medicine, Haihe Hospital, Tianjin University, Tianjin 300350, China., Xu G; Tianjin Key Laboratory of Lung Regenerative Medicine, Haihe Hospital, Tianjin University, Tianjin 300350, China., Wang Q; Department of Stomatology, Haihe Hospital, Tianjin University, Tianjin 300350, China., Ma Q; Department of Laboratory Medicine, Tianjin Hospital, Tianjin University, Tianjin 300350, China., Liu X; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Women's Guild Lung Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA., Li H; Department of Respiratory and Critical Care, Haihe Hospital, Tianjin University, Tianjin 300350, China., Wang S; Department of Respiratory, Tianjin Union Medical Center, Nankai University, Tianjin 300121, China., Liu Y; Tianjin Key Laboratory of Lung Regenerative Medicine, Haihe Hospital, Tianjin University, Tianjin 300350, China., Jin Y; State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071, China., Miao X; Department of Basic Medicine, Haihe Clinical School, Tianjin Medical University, Tianjin 300350, China., He Z; Department of Basic Medicine, Haihe Clinical School, Tianjin Medical University, Tianjin 300350, China., Dong J; Academy of Medical Engineering and Translational Medicine, School of Medicine, Tianjin University, Tianjin 300072, China., Li K; Tianjin Key Laboratory of Lung Regenerative Medicine, Haihe Hospital, Tianjin University, Tianjin 300350, China., Wang J; Tianjin Key Laboratory of Lung Regenerative Medicine, Haihe Hospital, Tianjin University, Tianjin 300350, China., Li Y; Tianjin Key Laboratory of Lung Regenerative Medicine, Haihe Hospital, Tianjin University, Tianjin 300350, China., Zhang Q; Tianjin Key Laboratory of Lung Regenerative Medicine, Haihe Hospital, Tianjin University, Tianjin 300350, China., Jiang D; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Women's Guild Lung Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA., Wu J; Tianjin Institute of Respiratory Diseases, Tianjin 300350, China. Electronic address: wujp0618@126.com., Ning W; State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071, China. Electronic address: ningwen108@nankai.edu.cn., Chen H; Tianjin Key Laboratory of Lung Regenerative Medicine, Haihe Hospital, Tianjin University, Tianjin 300350, China; Tianjin Institute of Respiratory Diseases, Tianjin 300350, China. Electronic address: huaiyong.chen@foxmail.com. |
| Πηγή: | Stem cell reports [Stem Cell Reports] 2026 Jul 14; Vol. 21 (7), pp. 102979. Date of Electronic Publication: 2026 Jul 02. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Cell Press Country of Publication: United States NLM ID: 101611300 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2213-6711 (Electronic) Linking ISSN: 22136711 NLM ISO Abbreviation: Stem Cell Reports Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: [Cambridge, MA] : Cell Press, c 2013- |
| Ιατρικοί όροι (MeSH): | Myofibroblasts*/metabolism , Myofibroblasts*/pathology , Autophagy-Related Protein 5*/deficiency , Autophagy-Related Protein 5*/genetics , Autophagy-Related Protein 5*/metabolism , Pulmonary Fibrosis*/pathology , Pulmonary Fibrosis*/metabolism , Pulmonary Fibrosis*/genetics , Pulmonary Alveoli*/pathology , Pulmonary Alveoli*/metabolism , Regeneration*, Transforming Growth Factor beta1/metabolism ; Alveolar Epithelial Cells/metabolism ; Idiopathic Pulmonary Fibrosis/pathology ; Idiopathic Pulmonary Fibrosis/metabolism ; Animals ; Cell Differentiation ; Humans ; Mice ; Bleomycin ; Oxidative Stress ; Cell Proliferation ; Cellular Senescence |
| Περίληψη: | Lung fibrosis progression is marked by impaired alveolar epithelial regeneration and uncontrolled myofibroblast differentiation, though the underlying mechanisms remain poorly understood. In this study, we discovered that Atg5 was upregulated in the mesenchymal cells of lungs from both patients with idiopathic pulmonary fibrosis (IPF) and mice with bleomycin (BLM)-induced fibrosis. Selective deletion of Atg5 in lung mesenchymal cells increased the susceptibility of mice to BLM-induced lung fibrosis. Mechanistically, the loss of Atg5 promoted transforming growth factor β 1 (TGF-β1)-induced oxidative stress and cellular senescence in fibroblasts, myofibroblast differentiation, and extracellular matrix deposition. Intriguingly, loss of Atg5 impaired the secretion of tissue repair-favoring factors in fibroblasts, causing defects in the proliferation and differentiation of alveolar type 2 cells. This study showed that Atg5 is essential for alveolar epithelial repair and myofibroblast control in lung fibrosis. (Copyright © 2026 The Author(s). Published by Elsevier Inc. All rights reserved.) |
| Competing Interests: | Declaration of interests The authors declare no competing interests. |
| Contributed Indexing: | Keywords: Tbx4; alveolar epithelial progenitor cells; myofibroblast differentiation; organoid cultures; pulmonary fibrosis |
| Substance Nomenclature: | 0 (Autophagy-Related Protein 5) 11056-06-7 (Bleomycin) 0 (Transforming Growth Factor beta1) |
| Entry Date(s): | Date Created: 20260702 Date Completed: 20260715 Latest Revision: 20260726 |
| Update Code: | 20260726 |
| PubMed Central ID: | PMC13385427 |
| DOI: | 10.1016/j.stemcr.2026.102979 |
| PMID: | 42392083 |
| Βάση Δεδομένων: | MEDLINE |
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