Glycochenodeoxycholic Acid Does Not Increase Transforming Growth Factor-Beta Expression in Bile Duct Epithelial Cells or Collagen Synthesis in Myofibroblasts

Background/aims: Primary sclerosing cholangitis (PSC) is a chronic, progressive hepatobiliary disorder characterized by extensive fibrosis and stricturing of the intra- and/or extra-hepatic bile ducts: Previous studies have documented low phosphatylcholine (PC) concentrations in PSC bile. The aim of this study was to determine whether low PC levels in bile facilitate toxic bile acid induced injury of biliary tract epithelial cells resulting in enhanced transforming growth factor-beta (TGF-β) expression and increased collagen synthesis by myofibroblasts.

Methods: TGF-β mRNA expression was documented in bile duct epithelial cells exposed to varying concentrations of the toxic bile acid; glycochenodeoxycholic acid (GCDCA) ± PC.

Results: In these experiments, as well as in co-culture experiments where bile duct epithelial cells were cultured with peripheral blood mononuclear cells and myofibroblasts, TGF-β mRNA expression remained unaltered in the presence or absence of PC. Moreover, collagen type Iα1 mRNA expression by myofibroblasts also remained unaltered.

Conclusion: The results of this study do not support the hypothesis that PC deficiency contributes to toxic bile acid-induced bile duct injury and/or myofibroblast activation.

DMEM, Dulbecco's modified Eagle medium; FBS, fetal bovine serum; GCDCA, glycochenodeoxycholic acid; PCR, Polymerase chain reaction; TGF-β, transforming growth factor-beta; bile acids; bile duct epithelial cells; fibrosis; phosphatylcholine; primary sclerosing cholangitis.