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Cytokine receptor\u2010like factor 1 (CRLF1) is a secreted protein with low or undetectable expression in normal physiology, but it is transcriptionally and translationally upregulated under pathological conditions. In this study, we found CRLF1 to be upregulated in the kidneys of patients with ATN and CKD, positively correlated with renal interstitial fibrosis, and negatively correlated with renal function. In vivo functional inhibition studies demonstrated that CRLF1 suppression significantly improved renal function, mitigated pathological damage, and delayed fibrosis progression in mouse models of IRI or UUO. Further in vitro studies revealed that CRLF1 promotes fibrosis and inflammation in renal tubular epithelial cells (TECs). Mechanistically, we employed chromatin immunoprecipitation (ChIP) to validate SMAD3 binding to the CRLF1 promoter and its transcriptional regulation, while elevated CRLF1 interacts with the VWFA domain of integrin \u03b21 (ITGB1). Furthermore, transcriptomic sequencing revealed that CRLF1 activates the PI3K\/AKT signaling pathway, promoting tubular epithelial cell fibrosis progression via ITGB1. These findings underscore the critical role of CRLF1 in renal fibrosis progression and suggest its potential as a therapeutic target for inhibiting the progression from AKI to CKD.<\/jats:p>","DOI":"10.1002\/advs.76896","type":"journal-article","created":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T21:48:32Z","timestamp":1785448112000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Renal Tubular Epithelial CRLF1 Interacts With ITGB1 to Accelerate Fibrosis During the Transition From AKI to CKD"],"prefix":"10.1002","author":[{"given":"Chunjie","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Nephrology Qilu Hospital of Shandong University  Jinan Shandong China"},{"name":"Laboratory of Basic Medical Sciences Qilu Hospital of Shandong University  Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Qilu Hospital Cheeloo College of Medicine and Institute of Brain and Brain\u2010Inspired Science Shandong University  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Bai","sequence":"additional","affiliation":[{"name":"Department of Nephrology Qilu Hospital of Shandong University  Jinan Shandong China"},{"name":"Laboratory of Basic Medical Sciences Qilu Hospital of Shandong University  Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shankui","family":"Qian","sequence":"additional","affiliation":[{"name":"Department of Nephrology Qilu Hospital of Shandong University  Jinan Shandong China"},{"name":"Laboratory of Basic Medical Sciences Qilu Hospital of Shandong University  Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Nephrology Qilu Hospital of Shandong University  Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangyi","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Nephrology Qilu Hospital of Shandong University  Jinan Shandong China"},{"name":"Laboratory of Basic Medical Sciences Qilu Hospital of Shandong University  Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiahui","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Nephrology Qilu Hospital of Shandong University  Jinan Shandong China"},{"name":"Laboratory of Basic Medical Sciences Qilu Hospital of Shandong University  Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuipeng","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Nephrology Qilu Hospital of Shandong University  Jinan Shandong China"},{"name":"Laboratory of Basic Medical Sciences Qilu Hospital of Shandong University  Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5504-9309","authenticated-orcid":false,"given":"Xiangdong","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Nephrology Qilu Hospital of Shandong University  Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,30]]},"reference":[{"issue":"3","key":"e_1_2_9_2_1","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1016\/j.kint.2018.04.011","article-title":"Analysis of the Global Burden of Disease Study Highlights the Global, Regional, and National Trends\u00a0of Chronic Kidney Disease Epidemiology from 1990 to 2016","volume":"94","author":"Xie Y.","year":"2016","journal-title":"Kidney International"},{"issue":"10302","key":"e_1_2_9_3_1","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1016\/S0140-6736(21)00519-5","article-title":"Chronic Kidney Disease","volume":"398","author":"Kalantar\u2010Zadeh K.","year":"2021","journal-title":"The Lancet"},{"issue":"1","key":"e_1_2_9_4_1","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1038\/s41392-023-01379-7","article-title":"Kidney Fibrosis: From Mechanisms to Therapeutic Medicines","volume":"8","author":"Huang R.","year":"2023","journal-title":"Signal Transduction and Targeted Therapy"},{"issue":"6","key":"e_1_2_9_5_1","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1007\/s40620-020-00793-2","article-title":"AKI: An Increasingly Recognized Risk Factor for CKD Development and pr Ogression","volume":"33","author":"Kurzhagen J. 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