Primary and Secondary Bile Acids Activate Hepatic Stellate Cells

The activation and proliferation of hepatic stellate cells (HSCs) is a major etiology contributing to the development and progression of liver fibrosis, cirrhosis and hepatocarcinogenesis. In response to liver injury, such as following oxidative stress, alcohol intoxication, viral infections and obesity, quiescent HSCs are transformed into an activated state. Cholestatic liver disease, which is generally characterized by the accumulation of bile acids in serum and liver, can progress to liver cirrhosis if not treated. However, the regulation of activation and proliferation of HSCs by bile acids is not fully understood. The current study was performed to determine the effects of two unconjugated primary bile acids [cholic acid (CA) and chenodeoxycholic acid (CDCA)] and one unconjugated secondary bile acid lithocholic acid (LCA) on the activation and proliferation of cultured human LX‐2 hepatic stellate cells. Our results showed that all of three bile acids induced activation and proliferation of LX‐2 cells, evidenced by increased mRNA expression of proliferating cell nuclear antigen (PCNA) and cytoglobin. In addition, all of three bile acids are predisposed to induce fibrogenesis as evidenced by increased mRNA expression of α‐smooth muscle actin (SMA) and procollagen‐1 in LX‐2 cells. In conclusion, both primary and secondary bile acids activate hepatic stellate cells and may consequently promote liver fibrogenesis.Support or Funding InformationDepartment of Pharmaceutical Sciences, St. John’s University, Queens, NY 11439, USA.