title: Bile acid receptor TGR5 overexpression is associated with decreased intestinal mucosal injury and epithelial cell proliferation in obstructive jaundice.
abstract: Bile acids stimulate intestinal epithelial proliferation in vitro. We sought to investigate the role of the bile acid receptor TGR5 in the protection of intestinal epithelial proliferation in obstructive jaundice. Intestinal tissues and serum samples were obtained from patients with malignant obstructive jaundice and from bile duct ligation (BDL) rats. Intestinal permeability and morphological changes in the intestinal mucosa were observed. The functions of TGR5 in cell proliferation in intestinal epithelial injury were determined by overexpression or knockdown studies in Caco-2 and FHs 74 Int cells pretreated with lipopolysaccharide (LPS). Internal biliary drainage was superior to external biliary drainage in recovering intestinal permeability and mucosal histology in patients with obstructive jaundice. In BDL rats, feeding of chenodeoxycholic acid (CDCA) decreased intestinal mucosa injury. The levels of PCNA, a marker of proliferation, increased in response to CDCA feeding and were paralleled by elevated TGR5 expression. CDCA upregulated TGR5 expression and promoted proliferation in Caco-2 and FHs 74 Int cells pretreated with LPS. Overexpression of TGR5 resulted in increased PCNA, cell viability, EdU incorporation, and the proportion of cells in S phase, whereas knockdown of TGR5 had the opposite effect. Our data indicate that bile acids promote intestinal epithelial cell proliferation and decrease mucosal injury by upregulating TGR5 expression in obstructive jaundice.
authors.affiliation: Department of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, Shijiazhuang, P. R. China; Department of Gastroenterology, The Third Hospital of Hebei Medical University, Shijiazhuang, P. R. China.
authors.forename: Chen-Guang
authors.initials: CG
authors.lastname: Ji
authors.affiliation: Department of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, Shijiazhuang, P. R. China.
authors.forename: Xiao-Li
authors.initials: XL
authors.lastname: Xie
authors.affiliation: Department of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, Shijiazhuang, P. R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Yin
authors.affiliation: Department of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, Shijiazhuang, P. R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Qi
authors.affiliation: Department of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, Shijiazhuang, P. R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, Shijiazhuang, P. R. China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Bai
authors.affiliation: Department of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, Shijiazhuang, P. R. China.
authors.forename: Na
authors.initials: N
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, Shijiazhuang, P. R. China.
authors.forename: Dong-Qiang
authors.initials: DQ
authors.lastname: Zhao
authors.affiliation: Department of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, Shijiazhuang, P. R. China.
authors.forename: Xiao-Yu
authors.initials: XY
authors.lastname: Jiang
authors.affiliation: Department of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, Shijiazhuang, P. R. China. Electronic address: jianghq@aliyun.com.
authors.forename: Hui-Qing
authors.initials: HQ
authors.lastname: Jiang
mesh_terms: D000368:Aged; D000818:Animals; D001652:Bile Ducts / Q000187:drug effects / Q000473:pathology; D015415:Biomarkers / Q000097:blood; D018938:Caco-2 Cells; D049109:Cell Proliferation / Q000187:drug effects; D002635:Chenodeoxycholic Acid / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects / Q000293:injuries* / Q000378:metabolism* / Q000473:pathology; D041781:Jaundice, Obstructive / Q000097:blood / Q000378:metabolism* / Q000473:pathology*; D008026:Ligation; D008070:Lipopolysaccharides; D008297:Male; D017207:Rats, Sprague-Dawley; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D015415:Biomarkers; C473772:GPBAR1 protein, human; C518268:Gpbar1 protein, rat; D008070:Lipopolysaccharides; D043562:Receptors, G-Protein-Coupled; D002635:Chenodeoxycholic Acid