Liver X Receptor beta and Peroxisome Proliferator-Activated Receptor delta Regulate Cholesterol Transport in Murine Cholangiocytes

doi:10.1002/hep.25919

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	Liver X Receptor beta and Peroxisome Proliferator-Activated Receptor delta Regulate Cholesterol Transport in Murine Cholangiocytes
	Xia, XF; Jung, DJ; Webb, P; Zhang, AJ; Zhang, B; Li, LF; Ayers, SD; Gabbi, C; Ueno, Y; Gustafsson, JA
刊名	HEPATOLOGY
	2012-12
卷号	56 期号:6 页码:2288-2296
ISSN号	0270-9139
DOI	10.1002/hep.25919
文献子类	Article
英文摘要	Nuclear receptors (NRs) play crucial roles in the regulation of hepatic cholesterol synthesis, metabolism, and conversion to bile acids, but their actions in cholangiocytes have not been examined. In this study, we investigated the roles of NRs in cholangiocyte physiology and cholesterol metabolism and flux. We examined the expression of NRs and other genes involved in cholesterol homeostasis in freshly isolated and cultured murine cholangiocytes and found that these cells express a specific subset of NRs, including liver X receptor (LXR) beta and peroxisome proliferator-activated receptor (PPAR) delta. Activation of LXR beta and/or PPAR delta in cholangiocytes induces ATP-binding cassette cholesterol transporter A1 (ABCA1) and increases cholesterol export at the basolateral compartment in polarized cultured cholangiocytes. In addition, PPAR delta induces Niemann-Pick C1-like L1 (NPC1L1), which imports cholesterol into cholangiocytes and is expressed on the apical cholangiocyte membrane via specific interaction with a peroxisome proliferator-activated response element (PPRE) within the NPC1L1 promoter. Conclusion: We propose that (1) LXR beta and PPAR delta coordinate NPC1L1/ABCA1-dependent vectorial cholesterol flux from bile through cholangiocytes and (2) manipulation of these processes may influence bile composition with important applications in cholestatic liver disease and gallstone disease, two serious health concerns for humans. (HEPATOLOGY 2012;56:2288-2296)
学科主题	Gastroenterology & Hepatology
出版地	HOBOKEN
资助项目	美国国立卫生研究院项目
项目编号	National Institutes of Health [R01 DK53366, RC4 DK90849, R01 DK54208, R01 DK062975] ; VA Merit Award
语种	英语
WOS记录号	WOS:000314288900061
资助机构	NIH
内容类型	期刊论文
源URL	[http://ir.lzu.edu.cn/handle/262010/125776]
专题	第一临床医学院_期刊论文
通讯作者	Xia, XF (reprint author), Methodist Hosp, Res Inst, Weill Cornell Sch Med, 6670 Bertner Ave,R8-117, Houston, TX 77030 USA.
推荐引用方式 GB/T 7714	Xia, XF,Jung, DJ,Webb, P,et al. Liver X Receptor beta and Peroxisome Proliferator-Activated Receptor delta Regulate Cholesterol Transport in Murine Cholangiocytes[J]. HEPATOLOGY,2012,56(6):2288-2296.
APA	Xia, XF.,Jung, DJ.,Webb, P.,Zhang, AJ.,Zhang, B.,...&Xia, XF .(2012).Liver X Receptor beta and Peroxisome Proliferator-Activated Receptor delta Regulate Cholesterol Transport in Murine Cholangiocytes.HEPATOLOGY,56(6),2288-2296.
MLA	Xia, XF,et al."Liver X Receptor beta and Peroxisome Proliferator-Activated Receptor delta Regulate Cholesterol Transport in Murine Cholangiocytes".HEPATOLOGY 56.6(2012):2288-2296.