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载脂蛋白 M 通过与 HepG2 细胞中的启动子区结合来调控孤儿核受体 LRH-1 基因表达

 

Authors Pan Y, Zhou HG, Zhou H, Hu M, Tang LJ

Published Date April 2015 Volume 2015:9 Pages 2375—2382

DOI http://dx.doi.org/10.2147/DDDT.S78496

Received 2 December 2014, Accepted 26 February 2015, Published 24 April 2015

Abstract: Apolipoprotein M (ApoM) is predominantly located in the high-density lipoprotein in human plasma. It has been demonstrated that ApoM expression could be regulated by several crucial nuclear receptors that are involved in the bile acid metabolism. In the present study, by combining gene-silencing experiments, overexpression studies, and chromatin immunoprecipitation assays, we showed that ApoM positively regulated liver receptor homolog-1 (LRH-1) gene expression via direct binding to an LRH-1  promoter region (nucleotides -406/-197). In addition, we investigated the effects of farnesoid X receptor agonist GW4064 on hepatic ApoM expression in vitro. In HepG2 cell cultures, both mRNA and protein levels of ApoM and LRH-1 were decreased in a time-dependent manner in the presence of 1 µM GW4064, and the inhibition effect was gradually attenuated after 24 hours. In conclusion, our findings present supportive evidence that ApoM is a regulator of human LRH-1 transcription, and further reveal the importance of ApoM as a critical regulator of bile acids metabolism.
Keywords: bile acids, chromatin immunoprecipitation assay, farnesoid X receptor, GW4064, high-density lipoprotein






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