Stellate Cell Activation and Imbalanced Expression of TGF- β 1/TGF- β 3 in Acute Autoimmune Liver Lesions Induced by ConA in Mice

Biomed Res Int. 2017:2017:2540540. doi: 10.1155/2017/2540540. Epub 2017 Jan 29.

Abstract

Objective. To study the pathogenic feature of liver injury, activation of hepatic stellate cells, and dynamic expression of TGF-β1/TGF-β3 to reveal their role in liver injury induced by ConA. Methods. Mice were randomly divided into control group and ConA treatment group. ConA (20 mg/kg) was injected through vena caudalis in ConA treatment group; the controls received the same volume of saline injection. After injection for 2 h, 8 h, 24 h, and 48 h, animals were terminated. Blood, liver, and spleen were harvested. Liver function and histopathology were studied. α-SMA, vimentin, TGF-β1, and TGF-β3 were detected. Results. After ConA injection, liver damage started to increase. Expression of α-SMA, vimentin, TGF-β1, and TGF-β3 was significantly enhanced; all above indicators reached peak at 8 h; but from 24 h after ConA injection, TGF-β3 expression began to decline, while the TGF-β1/TGF-β3 ratio at 48 h was significantly lower than control. Conclusion. (1) Autoimmune liver injury induced by ConA showed time-based features, in which the most serious liver lesions happened at 8 h after ConA injection. (2) Early activation of HSC and imbalance expression of TGF-β1 and TGF-β3 existed in ConA-induced acute autoimmune liver injury, which may be associated with liver dysfunction and the mechanisms of progression to fibrosis.

MeSH terms

  • Acute Disease
  • Animals
  • Autoimmune Diseases / blood
  • Autoimmune Diseases / metabolism
  • Autoimmune Diseases / pathology*
  • Autoimmune Diseases / physiopathology
  • Biomarkers / metabolism
  • Concanavalin A
  • Female
  • Hepatic Stellate Cells / metabolism*
  • Hepatic Stellate Cells / pathology*
  • Immunohistochemistry
  • Injections, Intravenous
  • Liver / enzymology
  • Liver / pathology*
  • Liver / physiopathology
  • Liver Function Tests
  • Mice
  • Spleen / pathology
  • Time Factors
  • Transaminases / metabolism
  • Transforming Growth Factor beta1 / blood
  • Transforming Growth Factor beta1 / metabolism*
  • Transforming Growth Factor beta3 / blood
  • Transforming Growth Factor beta3 / metabolism*
  • Vimentin / metabolism

Substances

  • Biomarkers
  • Transforming Growth Factor beta1
  • Transforming Growth Factor beta3
  • Vimentin
  • Concanavalin A
  • Transaminases