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. |
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