{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T20:36:03Z","timestamp":1774902963194,"version":"3.50.1"},"reference-count":24,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2020,7,2]],"date-time":"2020-07-02T00:00:00Z","timestamp":1593648000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007496","name":"Biomedical Laboratory Research and Development, VA Office of Research and Development","doi-asserted-by":"publisher","award":["BX000849"],"award-info":[{"award-number":["BX000849"]}],"id":[{"id":"10.13039\/100007496","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007496","name":"Biomedical Laboratory Research and Development, VA Office of Research and Development","doi-asserted-by":"publisher","award":["BX004127"],"award-info":[{"award-number":["BX004127"]}],"id":[{"id":"10.13039\/100007496","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Hepatic fibrosis is the accumulation of excess collagen as a result of chronic liver injury. If left unabated, hepatic fibrosis can lead to the disruption of the liver architecture, portal hypertension, and increased risk of progression to cirrhosis and hepatocellular carcinoma. The thiazolidinedione class of antidiabetic drugs, through their target peroxisome proliferator-activated receptor \u03b3 (PPAR\u03b3), have protective effects against liver fibrosis, and can inhibit the profibrotic activity of hepatic stellate cells, the major collagen-producing liver cells. However, these drugs have been ineffective in the treatment of established fibrosis, possibly due to side effects such as increased weight and adiposity. Recently, selective PPAR\u03b3 modulators that lack these side effects have been identified, but their role in treating fibrosis has not been studied. In this study, we tested the effectiveness of one of these selective modulators, SR1664, in the mouse carbon tetrachloride model of established hepatic fibrosis. Treatment with SR1664 reduced the total and type 1 collagen content without increasing body weight. The abundance of activated hepatic stellate cells was also significantly decreased. Finally, SR1664 inhibited the profibrotic phenotype of hepatic stellate cells. In summary, a selective PPAR\u03b3 modulator was effective in the reduction of established hepatic fibrosis and the activated phenotype of hepatic stellate cells. This may represent a new treatment approach for hepatic fibrosis.<\/jats:p>","DOI":"10.3390\/biology9070151","type":"journal-article","created":{"date-parts":[[2020,7,3]],"date-time":"2020-07-03T06:51:20Z","timestamp":1593759080000},"page":"151","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["A Selective PPAR\u03b3 Modulator Reduces Hepatic Fibrosis"],"prefix":"10.3390","volume":"9","author":[{"given":"Benita L.","family":"McVicker","sequence":"first","affiliation":[{"name":"Research Service, VA Nebraska-Western Iowa Health Care System, Omaha, NE 68105, USA"},{"name":"Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4911-9876","authenticated-orcid":false,"given":"Frederick G.","family":"Hamel","sequence":"additional","affiliation":[{"name":"Research Service, VA Nebraska-Western Iowa Health Care System, Omaha, NE 68105, USA"},{"name":"Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA"},{"name":"Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ronda L.","family":"Simpson","sequence":"additional","affiliation":[{"name":"Research Service, VA Nebraska-Western Iowa Health Care System, Omaha, NE 68105, USA"},{"name":"Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0755-6103","authenticated-orcid":false,"given":"Robert G.","family":"Bennett","sequence":"additional","affiliation":[{"name":"Research Service, VA Nebraska-Western Iowa Health Care System, Omaha, NE 68105, USA"},{"name":"Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA"},{"name":"Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,7,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S15","DOI":"10.1016\/j.jhep.2015.02.039","article-title":"Hepatic fibrosis: Concept to treatment","volume":"62","author":"Trautwein","year":"2015","journal-title":"J. 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