机构：[1]Department of Plastic Surgery, The Union Hospital of Fujian Medical University, 29 Xinquan Road, Fuzhou, Fujian, 350001, China,[2]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,四川大学华西医院[3]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,[4]Central Laboratory, Henan People's Hospital and Zhengzhou University People's Hospital, No.7 Wei Wu Road, Zhengzhou, Henan, 450003, China
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.
基金：
This work is supported partially by the
National Natural Science Foundation of China-Grant
No. 81372092, Fujian Natural Science Foundation-
Grant No. 2011J01173, Fujian Municipal Natural
Science Foundation-Grant No. 2011Y0029,
Foundation of Fujian Educational Committee
National-Grant No. JA11122 to X.C., National Natural
Science Foundation of China-Grant No. 81441121 to
X.F., and National Cancer Institute-Grant No. R01-
139158 to W.H.
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2015]版：
大类|3 区生物
小类|3 区综合性期刊
最新[2023]版：
大类|3 区综合性期刊
小类|3 区综合性期刊
第一作者：
第一作者机构：[1]Department of Plastic Surgery, The Union Hospital of Fujian Medical University, 29 Xinquan Road, Fuzhou, Fujian, 350001, China,
通讯作者：
推荐引用方式(GB/T 7714)：
Xiaosong Chen,Haixia Xu,Lili Ding,et al.Identification of miR-26a as a target gene of bile acid receptor GPBAR-1/TGR5.[J].PloS one.2015,10(6):e0131294.doi:10.1371/journal.pone.0131294.
APA：
Xiaosong Chen,Haixia Xu,Lili Ding,Guiyu Lou,Yan Liu...&Xianghui Fu.(2015).Identification of miR-26a as a target gene of bile acid receptor GPBAR-1/TGR5..PloS one,10,(6)
MLA：
Xiaosong Chen,et al."Identification of miR-26a as a target gene of bile acid receptor GPBAR-1/TGR5.".PloS one 10..6(2015):e0131294
