{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T18:56:25Z","timestamp":1790016985597,"version":"4.0.1"},"reference-count":34,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2019,8,6]],"date-time":"2019-08-06T00:00:00Z","timestamp":1565049600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Despite the wide use of angiotensin II receptor blockers in the treatment of Alport syndrome (AS), the mechanism as to how angiotensin II receptor blockers prevent interstitial fibrosis remains unclear. Here, we report that treatment of olmesartan effectively targets the feedback loop between the renin\u2013angiotensin system (RAS) and transforming growth factor \u03b2 (TGF\u03b2) signals in tubular epithelial cells and preserves renal angiotensin-converting enzyme 2 (ACE2) expression in the kidney of Col4a3\u2013\/\u2013 mice, a murine model of experimental AS. Morphology analyses revealed amelioration of kidney fibrosis in Col4a3\u2013\/\u2013 mice by olmesartan treatment. Upregulation of TGF\u03b2 and activation of its downstream in Col4a3\u2013\/\u2013 mice were attenuated by olmesartan in Col4a3\u2013\/\u2013 mice. Intriguingly, TGF\u03b2 expression was preferentially upregulated in damaged tubular epithelial cells in Col4a3\u2013\/\u2013 mice. Concurrent upregulation of TNF\u03b1-converting enzyme and downregulation of ACE2 suggested RAS activation in Col4a3\u2013\/\u2013 mice, which was prevented by olmesartan. Mechanistically, olmesartan suppressed TGF\u03b2-induced RAS activation in tubular epithelial cells in vitro. Collectively, we concluded that olmesartan effectively suppresses the progression of tubulointerstitial fibrosis in AS by interrupting RAS-TGF\u03b2 feedback loop to counterbalance intrarenal RAS activation.<\/jats:p>","DOI":"10.3390\/ijms20153843","type":"journal-article","created":{"date-parts":[[2019,8,7]],"date-time":"2019-08-07T03:09:08Z","timestamp":1565147348000},"page":"3843","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Olmesartan Attenuates Kidney Fibrosis in a Murine Model of Alport Syndrome by Suppressing Tubular Expression of TGF\u03b2"],"prefix":"10.3390","volume":"20","author":[{"given":"Sang Heon","family":"Suh","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Chonnam National University Hospital, Gwangju 61469, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8191-4071","authenticated-orcid":false,"given":"Hong Sang","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Chonnam National University Hospital, Gwangju 61469, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8753-7641","authenticated-orcid":false,"given":"Chang Seong","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Chonnam National University Hospital, Gwangju 61469, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"In Jin","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Chonnam National University Hospital, Gwangju 61469, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seong Kwon","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Chonnam National University Hospital, Gwangju 61469, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James W.","family":"Scholey","sequence":"additional","affiliation":[{"name":"Department of Medicine and Institute of Medical Science, University of Toronto, Toronto, NO M5S, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3540-9004","authenticated-orcid":false,"given":"Soo Wan","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Chonnam National University Hospital, Gwangju 61469, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1727-2822","authenticated-orcid":false,"given":"Eun Hui","family":"Bae","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Chonnam National University Hospital, Gwangju 61469, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,8,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2543","DOI":"10.1056\/NEJMra022296","article-title":"Alport\u2019s Syndrome, Goodpasture\u2019s Syndrome, and Type IV Collagen","volume":"348","author":"Hudson","year":"2003","journal-title":"New Engl. 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