The emerging role of AMP-activated protein kinase in cholestatic liver diseases

被引:20
作者
Li, Xiaojiaoyang [1 ,2 ]
Liu, Runping [2 ]
Zhang, Luyong [1 ,3 ]
Jiang, Zhenzhou [1 ,4 ]
机构
[1] China Pharmaceut Univ, Jiangsu Key Lab Drug Screening, Nanjing, Jiangsu, Peoples R China
[2] Virginia Commonwealth Univ, Dept Microbiol & Immunol, Richmond, VA 23298 USA
[3] Guangdong Pharmaceut Univ, Sch Pharm, Ctr Drug Screening & Pharmacodynam Evaluat, Guangzhou, Guangdong, Peoples R China
[4] China Pharmaceut Univ, Key Lab Drug Qual Control & Pharmacovigilance, Minist Educ, Nanjing, Jiangsu, Peoples R China
基金
中国国家自然科学基金;
关键词
AMP-activated protein kinase; Cholestasis; Fibrosis; Liver injury; FARNESOID X RECEPTOR; BILE-ACID-HOMEOSTASIS; HEPATIC STELLATE CELLS; 17-ALPHA-ETHINYLESTRADIOL-INDUCED CHOLESTASIS; OBSTRUCTIVE-CHOLESTASIS; INTESTINAL MICROBIOTA; INSULIN-RESISTANCE; SIGNALING PATHWAY; IN-VIVO; INJURY;
D O I
10.1016/j.phrs.2017.09.002
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
AMP-activated protein kinase (AMPK), recognized as an energy sensor with three heterotrimeric subunits (alpha, beta and gamma), not only maintains basal intracellular adenosine triphosphate levels but also regulates energy-intensive pathological responses, such as neurodegenerative and metabolic diseases, through multiple signaling pathways. Recent studies open a new direction for AMPK research and demonstrate that AMPK is a critical player in the pathogenesis of cholestatic liver injury and plays paradoxical roles in the regulation of different pathological processes, including the disruption of bile acid homeostasis and the regulation of hepatic polarity, inflammation and fibrosis. In the present review, we summarize recent findings that implicate AMPK-mediated signaling pathways in the pathogenesis of cholestatic liver injury. These findings provide novel insight regarding the potential use of AMPK as a therapeutic target for the treatment of cholestatic liver injury. (C) 2017 Elsevier Ltd. All rights reserved.
引用
收藏
页码:105 / 113
页数:9
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