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Transl. Med."],"published-print":{"date-parts":[[2026,2,18]]},"abstract":"<jats:p>\n                    The core of organ fibrosis formation lies in the regenerative defects of parenchymal cells and in the excessive activation of fibroblasts, yet methods to simultaneously address these pathological cell types remain lacking. Here, we found that the expression of the chaperone-mediated autophagy (CMA) limiting factor lysosome-associated membrane protein type 2A (LAMP2A) was consistently down-regulated in mouse models of bleomycin-induced pulmonary fibrosis, carbon tetrachloride (CCl\n                    <jats:sub>4<\/jats:sub>\n                    )\u2013induced liver fibrosis, and folic acid\u2013induced renal fibrosis. We also confirmed a low CMA score in patients with idiopathic pulmonary fibrosis, renal fibrosis, systemic sclerosis, and myocardial fibrosis. In the three mouse models, recombinant adeno-associated virus\u2013mediated overexpression of\n                    <jats:italic toggle=\"yes\">Lamp2a<\/jats:italic>\n                    was sufficient to inhibit the initiation and progression of fibrosis. Mechanistically, we demonstrated that LAMP2A overexpression in cultured fibroblast cell lines and each of the three mouse models could suppress fibroblast activation and reverse established myofibroblast fates by directly degrading the mechanosensitive protein integrin subunit beta 1. In addition, through cell type\u2013specific\n                    <jats:italic toggle=\"yes\">Lamp2a<\/jats:italic>\n                    overexpression in these fibrotic mouse models, we found that LAMP2A could promote regeneration in the liver, lungs, and kidneys. Moreover, pharmacological activation of CMA in these mouse models also alleviated organ fibrosis and promoted functional recovery when fibrosis had already been established. Thus, our study identifies LAMP2A as a broad-spectrum antifibrotic factor and provides proof of principle for dual targeting of core fibrotic cells to treat fibrosis.\n                  <\/jats:p>","DOI":"10.1126\/scitranslmed.ads9597","type":"journal-article","created":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T18:58:48Z","timestamp":1771441128000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":3,"title":["Chaperone-mediated autophagy supports organ regeneration and fibroblast quiescence in mouse models of fibrosis"],"prefix":"10.1126","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2362-2884","authenticated-orcid":true,"given":"Jiazhen","family":"Wang","sequence":"first","affiliation":[{"name":"Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases Co-Constructed by Henan Province and Education Ministry of People\u2019s Republic of China, Henan University of Chinese Medicine, Zhengzhou 450046, China."},{"name":"Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou 450046, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-1514-3502","authenticated-orcid":true,"given":"Ru","family":"Wang","sequence":"additional","affiliation":[{"name":"Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases Co-Constructed by Henan Province and Education Ministry of People\u2019s Republic of China, Henan University of Chinese Medicine, Zhengzhou 450046, China."},{"name":"Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou 450046, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-7040-8015","authenticated-orcid":true,"given":"Yang","family":"Liu","sequence":"additional","affiliation":[{"name":"Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases Co-Constructed by Henan Province and Education Ministry of People\u2019s Republic of China, Henan University of Chinese Medicine, Zhengzhou 450046, China."},{"name":"Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou 450046, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3701-9413","authenticated-orcid":true,"given":"Yicun","family":"Li","sequence":"additional","affiliation":[{"name":"Peking University Shenzhen Hospital, Shenzhen Peking University\u2013Hong Kong University of Science and Technology Medical Center, Shenzhen 518036, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Xian","sequence":"additional","affiliation":[{"name":"Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases Co-Constructed by Henan Province and Education Ministry of People\u2019s Republic of China, Henan University of Chinese Medicine, Zhengzhou 450046, China."},{"name":"Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou 450046, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanhang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases Co-Constructed by Henan Province and Education Ministry of People\u2019s Republic of China, Henan University of Chinese Medicine, Zhengzhou 450046, China."},{"name":"Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou 450046, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinning","family":"Zhang","sequence":"additional","affiliation":[{"name":"Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases Co-Constructed by Henan Province and Education Ministry of People\u2019s Republic of China, Henan University of Chinese Medicine, Zhengzhou 450046, China."},{"name":"Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou 450046, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayi","family":"Wang","sequence":"additional","affiliation":[{"name":"Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases Co-Constructed by Henan Province and Education Ministry of People\u2019s Republic of China, Henan University of Chinese Medicine, Zhengzhou 450046, China."},{"name":"Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou 450046, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-8859-4997","authenticated-orcid":true,"given":"Chuangeng","family":"Tu","sequence":"additional","affiliation":[{"name":"Zhongjing School, Henan University of Chinese Medicine, Zhengzhou 450046, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9394-9383","authenticated-orcid":true,"given":"Haojian","family":"Zhang","sequence":"additional","affiliation":[{"name":"Frontier Science Center for Immunology and Metabolism, Medical Research Institute, Wuhan University, Wuhan 430071, China."},{"name":"Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan 430071, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6485-2371","authenticated-orcid":true,"given":"Jiansheng","family":"Li","sequence":"additional","affiliation":[{"name":"Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases Co-Constructed by Henan Province and Education Ministry of People\u2019s Republic of China, Henan University of Chinese Medicine, Zhengzhou 450046, China."},{"name":"Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou 450046, 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