{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:31:22Z","timestamp":1789605082318,"version":"build-2803163510"},"reference-count":41,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T00:00:00Z","timestamp":1767139200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2021A1515012175"],"award-info":[{"award-number":["2021A1515012175"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2024A1515010402"],"award-info":[{"award-number":["2024A1515010402"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Tubulointerstitial fibrosis (TIF) significantly contributes to the development of end\u2010stage renal disease (ESRD) in chronic kidney disease (CKD). However, the underlying mechanisms driving its development remain poorly understood, thereby impeding the development of effective prevention and treatment strategies. Although growth differentiation factor 15 (GDF15) has been implicated in kidney diseases, its specific relationship and mechanisms in the context of renal TIF remain unclear. In this study, we investigated the role and mechanisms of GDF15 in TIF using a mouse model of unilateral ureteral obstruction (UUO) and human tubular epithelial cells (HK2) stimulated by transforming growth factor\u2010\u03b21 (TGF\u2010\u03b21). Our findings demonstrated a downregulation of GDF15 expression in TIF. The upregulation of GDF15 mitigates renal TIF and reduces macrophage infiltration, whereas its downregulation exacerbates these conditions. Further analysis revealed that GDF15 promotes autophagy and lysosome biogenesis via the PI3K\/Akt\/mTOR signalling pathway, conferring a protective effect against TIF. In summary, our study demonstrated a negative correlation between GDF15 expression and renal TIF, highlighting its protective role in TIF. Moreover, GDF15 was found to promote autophagy and resolution of TIF through the PI3K\/Akt\/mTOR signalling pathway.<\/jats:p>","DOI":"10.1111\/jcmm.70951","type":"journal-article","created":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T13:31:47Z","timestamp":1767187907000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Novel Roles of\n                    <scp>GDF15<\/scp>\n                    in Alleviating Renal Fibrosis: Promoting Autophagy and Lysosome Biogenesis via Inhibition of the\n                    <scp>PI3K<\/scp>\n                    \/Akt\/\n                    <scp>mTOR<\/scp>\n                    Pathway"],"prefix":"10.1111","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5644-372X","authenticated-orcid":false,"given":"Youqi","family":"Li","sequence":"first","affiliation":[{"name":"Department of Nephrology Huizhou Central People's Hospital  Huizhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinge","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Zhujiang Hospital Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danping","family":"Tao","sequence":"additional","affiliation":[{"name":"Department of Gerontology, Zhujiang Hospital Southern Medical University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoyang","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Sun Yat\u2010Sen Memorial Hospital Sun Yat\u2010Sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Yang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Prevention and Management of Chronic Kidney Disease of Zhanjiang City, Institute of Nephrology Affiliated Hospital of Guangdong Medical University  Zhanjiang Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongjun","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Nephrology Huizhou Central People's Hospital  Huizhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengwen","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Nephrology Huizhou Central People's Hospital  Huizhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boxun","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Nephrology Huizhou Central People's Hospital  Huizhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Zhujiang Hospital Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,12,31]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2012.39"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mam.2018.06.002"},{"issue":"9","key":"e_1_2_9_4_1","doi-asserted-by":"crossref","first-page":"4337","DOI":"10.1016\/S0021-9258(17)35666-1","article-title":"Transforming Growth Factor\u2010Beta Stimulates the Expression of Fibronectin and Collagen and Their Incorporation Into the Extracellular Matrix","volume":"261","author":"Ignotz R. 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