{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T22:28:50Z","timestamp":1791152930651,"version":"4.1.0"},"reference-count":25,"publisher":"National Academy of Sciences","issue":"21","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2012,5,22]]},"abstract":"<jats:p>\n                    Peroxisome proliferator-activated receptor delta (PPAR\u03b4), a member of the nuclear receptor family, is emerging as a key metabolic regulator with pleiotropic actions on various tissues including fat, skeletal muscle, and liver. Here we show that the PPAR\u03b4 agonist KD3010, but not the well-validated GW501516, dramatically ameliorates liver injury induced by carbon tetrachloride (CCl\n                    <jats:sub>4<\/jats:sub>\n                    ) injections. Deposition of extracellular matrix proteins was lower in the KD3010-treated group than in the vehicle- or GW501516-treated group. Interestingly, profibrogenic connective tissue growth factor was induced significantly by GW501516, but not by KD3010, following CCl\n                    <jats:sub>4<\/jats:sub>\n                    treatment. The hepatoprotective and antifibrotic effect of KD3010 was confirmed in a model of cholestasis-induced liver injury and fibrosis using bile duct ligation for 3 wk. Primary hepatocytes treated with KD3010 but not GW501516 were protected from starvation or CCl\n                    <jats:sub>4<\/jats:sub>\n                    -induced cell death, in part because of reduced reactive oxygen species production. In conclusion, our data demonstrate that an orally active PPAR\u03b4 agonist has hepatoprotective and antifibrotic effects in animal models of liver fibrosis, suggesting a possible mechanistic and therapeutic approach in treating patients with chronic liver diseases.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1202464109","type":"journal-article","created":{"date-parts":[[2012,4,26]],"date-time":"2012-04-26T20:49:36Z","timestamp":1335473376000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":149,"title":["Protection from liver fibrosis by a peroxisome proliferator-activated receptor \u03b4 agonist"],"prefix":"10.1073","volume":"109","author":[{"given":"Keiko","family":"Iwaisako","sequence":"first","affiliation":[{"name":"Departments of aMedicine and"},{"name":"Radiology, University of California at San Diego, La Jolla, CA 92093;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Haimerl","sequence":"additional","affiliation":[{"name":"Departments of aMedicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong-Han","family":"Paik","sequence":"additional","affiliation":[{"name":"Departments of aMedicine and"},{"name":"Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135-710, Korea; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kojiro","family":"Taura","sequence":"additional","affiliation":[{"name":"Departments of aMedicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuzo","family":"Kodama","sequence":"additional","affiliation":[{"name":"Departments of aMedicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claude","family":"Sirlin","sequence":"additional","affiliation":[{"name":"Radiology, University of California at San Diego, La Jolla, CA 92093;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Yu","sequence":"additional","affiliation":[{"name":"Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth T.","family":"Yu","sequence":"additional","affiliation":[{"name":"Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Downes","sequence":"additional","affiliation":[{"name":"Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald M.","family":"Evans","sequence":"additional","affiliation":[{"name":"Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Brenner","sequence":"additional","affiliation":[{"name":"Departments of aMedicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernd","family":"Schnabl","sequence":"additional","affiliation":[{"name":"Departments of aMedicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2012,4,25]]},"reference":[{"key":"e_1_1_2_17_8_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncpgasthep1200"},{"key":"e_1_1_2_17_8_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(03)00104-7"},{"key":"e_1_3_4_1_2","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1172\/JCI24282","article-title":"Liver fibrosis","volume":"115","author":"Bataller R","year":"2005","unstructured":"R Bataller, DA Brenner, Liver fibrosis. 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