title: Retinoic acid regulates several genes in bile acid and lipid metabolism via upregulation of small heterodimer partner in hepatocytes.
abstract: Retinoic acid (RA) affects multiple aspects of development, embryogenesis and cell differentiation processes. The liver is a major organ that stores RA suggesting that retinoids play an important role in the function of hepatocytes. In our previous studies, we have demonstrated the involvement of small heterodimer partner (SHP) in RA-induced signaling in a non-transformed hepatic cell line AML 12. In the present study, we have identified several critical genes in lipid homeostasis (Apoa1, Apoa2 and ApoF) that are repressed by RA-treatment in a SHP dependent manner, in vitro and also in vivo with the use of the SHP null mice. In a similar manner, RA also represses several critical genes involved in bile acid metabolism (Cyp7a1, Cyp8b1, Mdr2, Bsep, Baat and Ntcp) via upregulation of SHP. Collectively our data suggest that SHP plays a major role in RA-induced potential changes in pathophysiology of metabolic disorders in the liver.
authors.affiliation: Department of Medicine, University of Mississippi Medical Center, Jackson, MS 39216, USA.
authors.forename: Abulkhair
authors.initials: A
authors.lastname: Mamoon
authors.affiliation: Department of Medicine, University of Mississippi Medical Center, Jackson, MS 39216, USA.
authors.forename: Angela
authors.initials: A
authors.lastname: Subauste
authors.affiliation: Department of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: Maria C
authors.initials: MC
authors.lastname: Subauste
authors.affiliation: G.V. (Sonny) Montgomery Veterans Affairs Medical Center, Jackson, MS 39216, USA.
authors.forename: Jose
authors.initials: J
authors.lastname: Subauste
mesh_terms: D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism*; D002478:Cells, Cultured; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects* / Q000235:genetics*; D008297:Male; D053858:Metabolic Networks and Pathways / Q000187:drug effects / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics* / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D001647:Bile Acids and Salts; D018160:Receptors, Cytoplasmic and Nuclear; C099713:nuclear receptor subfamily 0, group B, member 2; D014212:Tretinoin
keywords: AML12 cell line; Retinoic acid; Small heterodimer partner