{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T08:30:34Z","timestamp":1789115434450,"version":"build-2803163510"},"reference-count":34,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2020,12,9]],"date-time":"2020-12-09T00:00:00Z","timestamp":1607472000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["FEBS Open Bio"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:p>Several studies have indicated that cholestatic liver damage involves mitochondria dysfunction. However, the precise mechanism by which hydrophobic bile salts cause mitochondrial dysfunction is not clear. In this study, we intended to determine the pathogenesis of cholestatic liver injury associated with peroxisome proliferator\u2010activated receptor\u2010\u03b3 co\u2010activator 1\u03b1 (PGC\u20101\u03b1). A mouse model of cholestatic liver disease was generated by surgical ligation of the bile duct (BDL), and a mouse model of fibrosis was developed through serial administration of thioacetamide. After obtaining liver specimens on scheduled days, we compared the expression of the antioxidant enzymes (superoxide dismutase 2 [SOD2], catalase, and glutathione peroxidase\u20101[GPx\u20101]) and PGC\u20101\u03b1 in livers from mice with fibrosis and cholestasis using western blotting, immunohistochemistry, and immunofluorescence. We found that cholestatic livers exhibit lower expression of antioxidant enzymes, such as SOD2, catalase, and PGC\u20101\u03b1. In contrast, fibrotic livers exhibit higher expression of antioxidant enzymes and PGC\u20101\u03b1. In addition, cholestatic livers exhibited significantly lower expression of pro\u2010apoptotic markers (Bax) as compared to fibrotic livers. It is well known that overexpression of PGC\u20101\u03b1 increases mitochondrial antioxidant enzyme expression, and vice versa. Thus, we concluded that obstructive cholestasis decreases expression of PGC\u20101\u03b1, which may lead to decreased expression of mitochondrial antioxidant enzymes, thereby rendering mice with cholestatic livers vulnerable to ROS\u2010induced cell death.<\/jats:p>","DOI":"10.1002\/2211-5463.12961","type":"journal-article","created":{"date-parts":[[2020,8,29]],"date-time":"2020-08-29T15:55:27Z","timestamp":1598716527000},"page":"61-74","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["PGC\u20101\u03b1 is downregulated in a mouse model of obstructive cholestasis but not in a model of liver fibrosis"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2693-0655","authenticated-orcid":false,"given":"Jung Hyun","family":"Park","sequence":"first","affiliation":[{"name":"Department of Surgery College of Medicine Eunpyeong St. Mary's Hospital the Catholic University of Korea Seoul 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