{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T13:29:38Z","timestamp":1783603778486,"version":"3.55.0"},"reference-count":52,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2020,2,21]],"date-time":"2020-02-21T00:00:00Z","timestamp":1582243200000},"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>Histone deacetylases have been a target of therapy for organ fibrosis. Here, we report the protective effect of CG200745 (CG), a novel histone deacetylase inhibitor, on tubulointerstitial fibrosis in Col4a3\u2212\/\u2212 mice, a murine model of Alport syndrome. Morphological analyses revealed CG treatment markedly alleviated kidney fibrosis in Col4a3\u2212\/\u2212 mice at the age of 7 weeks. CG prevented the activation of transforming growth factor \u03b2 (TGF\u03b2) and its downstream SMAD signaling in the kidney of Col4a3\u2212\/\u2212 mice. As critical upstream regulators of TGF\u03b2 signaling, immunoblotting of whole kidney lysate of Col4a3\u2212\/\u2212 mice reveled that intra-renal renin\u2013angiotensin system (RAS) was activated with concurrent upregulation of inflammation and apoptosis, which were effectively suppressed by CG treatment. CG suppressed both activation of RAS and up-regulation of TGF\u03b2 signals in angiotensin II-stimulated HK-2 cells, a human kidney proximal tubular epithelial cell line. CG inhibited activation of TGF\u03b2-driven signals and fibrosis in NRK-49F cells, a rat kidney fibroblast cell line, under angiotensin II-rich conditions. Collectively, CG was found to be effective both in proximal tubular epithelial cells by inhibiting local RAS and TGF\u03b2 signaling activation, as well as in fibroblasts by blocking their transition to myofibroblasts, attenuating renal fibrosis in a murine model of Alport syndrome.<\/jats:p>","DOI":"10.3390\/ijms21041473","type":"journal-article","created":{"date-parts":[[2020,2,21]],"date-time":"2020-02-21T10:49:16Z","timestamp":1582282156000},"page":"1473","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["CG200745, a Novel HDAC Inhibitor, Attenuates Kidney Fibrosis in a Murine Model of Alport Syndrome"],"prefix":"10.3390","volume":"21","author":[{"given":"Sang Heon","family":"Suh","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Chonnam National University Medical School, Gwangju 61469, Korea"},{"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 Medical School, Gwangju 61469, Korea"},{"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 Medical School, Gwangju 61469, Korea"},{"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 Medical School, Gwangju 61469, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4768-0608","authenticated-orcid":false,"given":"Hyunju","family":"Cha","sequence":"additional","affiliation":[{"name":"Crystal Genomics, Inc., 5 F, Bldg A, Korea Bio Park, Seongnam 13488, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joong Myung","family":"Cho","sequence":"additional","affiliation":[{"name":"Crystal Genomics, Inc., 5 F, Bldg A, Korea Bio Park, Seongnam 13488, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seong Kwon","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Chonnam National University Medical School, Gwangju 61469, Korea"},{"name":"Department of Internal Medicine, Chonnam National University Hospital, Gwangju 61469, Korea"}],"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 Medical School, Gwangju 61469, Korea"},{"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 Medical School, Gwangju 61469, Korea"},{"name":"Department of Internal Medicine, Chonnam National University Hospital, Gwangju 61469, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,2,21]]},"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":"N. 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