title: Identification of miR-26a as a target gene of bile acid receptor GPBAR-1/TGR5.
abstract: GPBAR1/TGR5 is a G protein-coupled receptor of bile acids. TGR5 is known to regulate the BA homeostasis and energy metabolism. Recent studies highlight an important role of TGR5 in alleviating obesity and improving glucose regulation, however, the mechanism of which is still unclear. Here we report that TGR5 is involved in mediating the anti-obesity and anti-hyperglycemia effect of a natural compound, oleanolic acid. By comparing the miRNA profiles between wild type and TGR5-/- livers after OA treatment, we identified miR-26a as a novel downstream target gene of TGR5 activation. The expression of miR-26a in the liver was induced in a TGR5-dependent manner after feeding the mice with a bile acid diet. TGR5 activation strongly increased the expression of miR-26a in macrophages, including the Kupffer cells in the liver. We further demonstrated that JNK pathway was required for miR-26a induction by TGR5 activation. Interestingly, we located the TGR5-responsive DNA element to a proximal region of miR-26's promoter, which was independent of the transcription of its host genes. These results unravel a new mechanism by which bile acid receptor TGR5 activates a miRNA gene expression.
authors.affiliation: Department of Plastic Surgery, The Union Hospital of Fujian Medical University, 29 Xinquan Road, Fuzhou, Fujian, 350001, China.
authors.forename: Xiaosong
authors.initials: X
authors.lastname: Chen
authors.affiliation: Division of Endocrinology and Metabolism, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, and Collaborative Innovation Center of Biotherapy, Chengdu, Sichuan, 610041, China.
authors.forename: Haixia
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Diabetes Complications and Metabolism, Diabetes & Metabolism Research Institute, Beckman Research Institute, City of Hope National Medical Center, 1500 Duarte Road, Duarte, CA, 91010, United States of America.
authors.forename: Lili
authors.initials: L
authors.lastname: Ding
authors.affiliation: Department of Diabetes Complications and Metabolism, Diabetes & Metabolism Research Institute, Beckman Research Institute, City of Hope National Medical Center, 1500 Duarte Road, Duarte, CA, 91010, United States of America; Central Laboratory, Henan People's Hospital and Zhengzhou University People's Hospital, No.7 Wei Wu Road, Zhengzhou, Henan, 450003, China.
authors.forename: Guiyu
authors.initials: G
authors.lastname: Lou
authors.affiliation: Department of Plastic Surgery, The Union Hospital of Fujian Medical University, 29 Xinquan Road, Fuzhou, Fujian, 350001, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Division of Endocrinology and Metabolism, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, and Collaborative Innovation Center of Biotherapy, Chengdu, Sichuan, 610041, China.
authors.forename: Yalan
authors.initials: Y
authors.lastname: Yao
authors.affiliation: Department of Plastic Surgery, The Union Hospital of Fujian Medical University, 29 Xinquan Road, Fuzhou, Fujian, 350001, China.
authors.forename: Liangwan
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Diabetes Complications and Metabolism, Diabetes & Metabolism Research Institute, Beckman Research Institute, City of Hope National Medical Center, 1500 Duarte Road, Duarte, CA, 91010, United States of America.
authors.forename: Wendong
authors.initials: W
authors.lastname: Huang
authors.affiliation: Division of Endocrinology and Metabolism, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, and Collaborative Innovation Center of Biotherapy, Chengdu, Sichuan, 610041, China.
authors.forename: Xianghui
authors.initials: X
authors.lastname: Fu
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D019440:Anti-Obesity Agents / Q000737:chemistry; D001647:Bile Acids and Salts / Q000378:metabolism; D045744:Cell Line, Tumor; D004247:DNA / Q000032:analysis; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D005951:Glucose Tolerance Test; D006801:Humans; D007004:Hypoglycemic Agents / Q000737:chemistry; D007555:Isoxazoles / Q000737:chemistry; D007728:Kupffer Cells / Q000166:cytology; D008099:Liver / Q000378:metabolism; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000502:physiology*; D009828:Oleanolic Acid / Q000737:chemistry; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*
chemical_list: D019440:Anti-Obesity Agents; D001647:Bile Acids and Salts; D004247:DNA; D007004:Hypoglycemic Agents; D007555:Isoxazoles; D048670:MAP Kinase Kinase 4; D035683:MicroRNAs; D009828:Oleanolic Acid; D043562:Receptors, G-Protein-Coupled; C473772:GPBAR1 protein, human; C513561:Gpbar1 protein, mouse; C528163:MIRN26 microRNA, human; C543693:Mirn26 microRNA, mouse; C412815:GW 4064