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LIM and senescent cell antigen\u2010like domains protein 1 (LIMS1) plays an essential role in controlling of cell behaviour through the formation of complexes with other proteins. Here, the function and regulation of LIMS1 in angiotensin II (Ang II)\u2010induced hypertension and tubulointerstitial fibrosis was investigated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>C57BL\/6 mice were treated with Ang II to induce tubulointerstitial fibrosis. Hypoxia\u2010inducible factor\u20101\u03b1 (HIF\u20101\u03b1) renal tubular\u2010specific knockout mice or LIMS1 knockdown AAV was used to investigate their effects on Ang II\u2010induced renal interstitial fibrosis. In vitro, HIF\u20101\u03b1 or LIMS1 was knocked down or overexpressed in HK2 cells after exposure to Ang II.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Increased expression of tubular LIMS1 was observed in human kidney with hypertensive nephropathy and in murine kidney from Ang II\u2010induced hypertension model. Tubular\u2010specific knockdown of LIMS1 ameliorated Ang II\u2010induced tubulointerstitial fibrosis in mice. Furthermore, we demonstrated that LIMS1 was transcriptionally regulated by HIF\u20101\u03b1 in tubular cells and that tubular HIF\u20101\u03b1 knockout ameliorates LIMS1\u2010mediated tubulointerstitial fibrosis. In addition, LIMS1 promotes Ang II\u2010induced tubulointerstitial fibrosis by interacting with vimentin.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and Implications<\/jats:title><jats:p>We conclude that HIF\u20101\u03b1 transcriptionally regulated LIMS1 plays a central role in Ang II\u2010induced tubulointerstitial fibrosis through interacting with vimentin. Our finding represents a new insight into the mechanism of Ang II\u2010induced tubulointerstitial fibrosis and provides a novel therapeutic target for progression of CKD.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.16358","type":"journal-article","created":{"date-parts":[[2024,5,3]],"date-time":"2024-05-03T07:31:15Z","timestamp":1714721475000},"page":"3098-3117","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["HIF\u20101\u03b1 and adaptor protein LIM and senescent cell antigen\u2010like domains protein 1 axis promotes tubulointerstitial fibrosis by interacting with vimentin in angiotensin II\u2010induced hypertension"],"prefix":"10.1111","volume":"181","author":[{"given":"Wei\u2010Jie","family":"Ni","sequence":"first","affiliation":[{"name":"Institute of Nephrology Zhong Da Hospital, Southeast University School of Medicine  Nanjing Jiangsu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6694-8406","authenticated-orcid":false,"given":"Zuo\u2010Lin","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Nephrology Zhong Da Hospital, Southeast University School of Medicine  Nanjing Jiangsu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xian\u2010Li","family":"Wen","sequence":"additional","affiliation":[{"name":"Department of Pediatrics The Second Affiliated Hospital of Nanjing Medical University  Nanjing Jiangsu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jia\u2010Ling","family":"Ji","sequence":"additional","affiliation":[{"name":"Department of Pediatrics The Fourth Affiliated Hospital of Nanjing Medical University  Nanjing Jiangsu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hong","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Nephrology Zhong Da Hospital, Southeast University School of Medicine  Nanjing Jiangsu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qing","family":"Yin","sequence":"additional","affiliation":[{"name":"Institute of Nephrology Zhong Da Hospital, Southeast University School of Medicine  Nanjing Jiangsu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liang\u2010Yun\u2010Zi","family":"Jiang","sequence":"additional","affiliation":[{"name":"Institute of Nephrology Zhong Da Hospital, Southeast University School of Medicine  Nanjing Jiangsu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi\u2010Lin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Nephrology Zhong Da Hospital, Southeast University School of Medicine  Nanjing Jiangsu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi","family":"Wen","sequence":"additional","affiliation":[{"name":"Institute of Nephrology Zhong Da Hospital, Southeast University School of Medicine  Nanjing Jiangsu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tao\u2010Tao","family":"Tang","sequence":"additional","affiliation":[{"name":"Institute of Nephrology Zhong Da Hospital, Southeast University School of Medicine  Nanjing Jiangsu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Jiang","sequence":"additional","affiliation":[{"name":"Institute of Nephrology Zhong Da Hospital, Southeast University School of Medicine  Nanjing Jiangsu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lin\u2010Li","family":"Lv","sequence":"additional","affiliation":[{"name":"Institute of Nephrology Zhong Da Hospital, Southeast University School of Medicine  Nanjing Jiangsu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei\u2010Hua","family":"Gan","sequence":"additional","affiliation":[{"name":"Department of Pediatrics The Second Affiliated Hospital of Nanjing Medical University  Nanjing Jiangsu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bi\u2010Cheng","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Nephrology Zhong Da Hospital, Southeast University School of Medicine  Nanjing Jiangsu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bin","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Nephrology Zhong Da Hospital, Southeast University School of Medicine  Nanjing Jiangsu China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,5,3]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00094.2014"},{"issue":"1","key":"e_1_2_12_3_1","first-page":"S1","article-title":"The concise guide to pharmacology 2021\/22: Introduction and Other Protein Targets","volume":"1","author":"Alexander S. 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