Clusterin Attenuates Hepatic Fibrosis by Inhibiting Hepatic Stellate Cell Activation and Downregulating the Smad3 Signaling Pathway

Cells. 2019 Nov 14;8(11):1442. doi: 10.3390/cells8111442.

Abstract

Clusterin is a glycoprotein that is expressed in most human tissues and found in body fluids. In our previous studies we demonstrated that clusterin has a protective effect against hepatic lipid accumulation and renal fibrosis; however, the role of clusterin in hepatic fibrosis is unknown. Here, we examined whether clusterin had protective effects against hepatic fibrosis using in vitro and in vivo models. Clusterin was upregulated in the livers of human cirrhotic patients and in thioacetamide (TAA)-induced and bile duct ligation mouse models of liver fibrosis. Loss and overexpression of clusterin promoted and attenuated hepatic fibrosis after TAA injection, respectively. In addition, we found that clusterin attenuates hepatic fibrosis by inhibiting the activation of hepatic stellate cells and Smad3 signaling pathways. Thus, clusterin plays an important role in hepatic fibrosis.

Keywords: Smad3; clusterin; hepatic fibrosis; hepatic stellate cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Clusterin / genetics*
  • Clusterin / metabolism
  • Disease Models, Animal
  • Down-Regulation
  • Gene Knockout Techniques
  • Hepatic Stellate Cells / cytology*
  • Hepatic Stellate Cells / metabolism
  • Humans
  • Liver Cirrhosis / chemically induced
  • Liver Cirrhosis / genetics
  • Liver Cirrhosis / metabolism*
  • Male
  • Mice
  • Signal Transduction
  • Smad3 Protein / metabolism*
  • Thioacetamide / adverse effects*
  • Up-Regulation

Substances

  • CLU protein, human
  • Clu protein, mouse
  • Clusterin
  • Smad3 Protein
  • Smad3 protein, mouse
  • Thioacetamide