https://scholars.lib.ntu.edu.tw/handle/123456789/521231
標題: | Increased Autophagy Markers Are Associated with Ductular Reaction during the Development of Cirrhosis | 作者: | Hung, Tzu-Min RAY-HWANG YUAN WEI-PANG HUANG Chen, Yu-Hsuan Lin, Yu-Chun Lin, Chih-Wen HONG-SHIEE LAI PO-HUANG LEE |
公開日期: | 2015 | 出版社: | Elsevier Inc. | 卷: | 185 | 期: | 9 | 起(迄)頁: | 2454-2467 | 來源出版物: | American Journal of Pathology | 摘要: | Autophagy is a regulatory pathway in liver fibrosis. We investigated the roles of autophagy in human cirrhotic livers. Cirrhotic and noncirrhotic liver tissues were obtained from patients with hepatocellular carcinoma, and liver tissues from live donors served as control. Patients with cirrhotic livers had significantly increased levels of various essential autophagy-related genes compared with noncirrhotic livers. In addition, colocalization of autophagy marker microtubule-associated protein 1 light chain 3B (LC3B) with lysosome-associated membrane protein-1, increased levels of lysosome-associated membrane protein-2, and increased maturation of lysosomal cathepsin D were observed in cirrhotic livers. By using dual-immunofluorescence staining, we demonstrated that increased LC3B was located mainly in the cytokeratin 19-labeled ductular reaction (DR) in human cirrhotic livers and in an experimental cirrhosis induced by 2-acetylaminofluorene (AAF) with carbon tetrachloride (CCl4), indicating a conserved response to chronic liver damage. Furthermore, an AAF/CCl4-mediated increase in DR and fibrosis were attenuated after chloroquine treatment, suggesting that the autophagy-lysosome pathway was essential for AAF/CCl4-induced DR-fibrosis. In conclusion, we demonstrated that increased autophagy marker positively correlated with DR during the development of cirrhosis. Therefore, targeting autophagy may hold therapeutic value for liver cirrhosis. © 2015 American Society for Investigative Pathology. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84941097911&doi=10.1016%2fj.ajpath.2015.05.010&partnerID=40&md5=66d6e216ea91644b928364043b88375a https://scholars.lib.ntu.edu.tw/handle/123456789/521231 |
ISSN: | 0002-9440 | DOI: | 10.1016/j.ajpath.2015.05.010 |
顯示於: | 醫學系 |
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