title: Apolipoprotein M regulates the orphan nuclear receptor LRH-1 gene expression through binding to its promoter region in HepG2 cells.
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.
authors.affiliation: Clinical Laboratory, The Second Xiangya Hospital of Central South University, Changsha, Hunan, People's Republic of China ; Molecular Biology Research Center, School of Life Sciences, Central South University, Changsha, Hunan, People's Republic of China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Pan
authors.affiliation: Clinical Laboratory, The Second Xiangya Hospital of Central South University, Changsha, Hunan, People's Republic of China.
authors.forename: Hou-gang
authors.initials: HG
authors.lastname: Zhou
authors.affiliation: Tumor Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, People's Republic of China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Clinical Laboratory, The Second Xiangya Hospital of Central South University, Changsha, Hunan, People's Republic of China.
authors.forename: Min
authors.initials: M
authors.lastname: Hu
authors.affiliation: Molecular Biology Research Center, School of Life Sciences, Central South University, Changsha, Hunan, People's Republic of China.
authors.forename: Li-jun
authors.initials: LJ
authors.lastname: Tang
mesh_terms: D001053:Apolipoproteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000075243:Apolipoproteins M; D001647:Bile Acids and Salts / Q000378:metabolism; D047369:Chromatin Immunoprecipitation; D005786:Gene Expression Regulation / Q000187:drug effects; D020868:Gene Silencing; D056945:Hep G2 Cells; D006801:Humans; D007555:Isoxazoles / Q000494:pharmacology; D054834:Lipocalins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008099:Liver / Q000378:metabolism; D010957:Plasmids / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists / Q000378:metabolism / Q000502:physiology*; D014162:Transfection; D000099150:Receptor, Farnesoid X-Activated
chemical_list: D001053:Apolipoproteins; D000075243:Apolipoproteins M; D001647:Bile Acids and Salts; D007555:Isoxazoles; D054834:Lipocalins; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D000099150:Receptor, Farnesoid X-Activated; C400523:APOM protein, human; C082631:NR5A2 protein, human; C412815:GW 4064
keywords: GW4064; bile acids; chromatin immunoprecipitation assay; farnesoid X receptor; high-density lipoprotein