Geranylgeranylacetone attenuates hepatic fibrosis by increasing the expression of heat shock protein 70

Mol Med Rep. 2015 Oct;12(4):4895-900. doi: 10.3892/mmr.2015.4069. Epub 2015 Jul 9.

Abstract

Increasing evidence has demonstrated that the heat shock protein 70 (HSP70) gene may be closely associated with tissue fibrosis; however, the association between HSP70 and liver fibrosis remains to be fully elucidated. The present study hypothesized that geranylgeranylacetone (GGA) exerts beneficial effects on liver fibrosis though upregulation of the expression of HSP70. Liver fibrosis was induced in rats using carbon tetrachloride (CCl4). The rats were subsequently divided into three groups: Control group, CCl4 model group and CCl4 model + GGA group. Liver fibrosis in the rats was evaluated using hematoxylin and eosin staining, Masson's trichrome staining and Sirius red staining. The levels of serum alanine aminotransferase, aspartate aminotransferase and total bilirubin were determined using an automated biochemistry analyzer. The levels of total hepatic hydroxyproline were also determined. The expression levels of α‑smooth muscle actin (α‑SMA) and transforming growth factor‑β1 (TGF‑β1) were determined using immunofluorescence staining and western blotting, and the protein expression levels of HSP70 were determined using western blotting. The CCl4‑induced rats exhibited liver fibrosis, increased hydroxyproline content, impaired liver function, upregulated expression levels of the α‑SMA and TGF‑β1 pro‑fibrogenic proteins, and increased expression of HSP70, compared with the control group. These changes were attenuated by treatment with GGA. These results demonstrated that GGA exerted beneficial effects in CCl4‑induced liver fibrosis via upregulating the expression of HSP70.

MeSH terms

  • Actins / metabolism
  • Alanine Transaminase / blood
  • Animals
  • Aspartate Aminotransferases / blood
  • Bilirubin / blood
  • Carbon Tetrachloride
  • Disease Models, Animal
  • Diterpenes / pharmacology*
  • HSP70 Heat-Shock Proteins / genetics
  • HSP70 Heat-Shock Proteins / metabolism*
  • Hydroxyproline / metabolism
  • Liver / metabolism
  • Liver Cirrhosis / chemically induced
  • Liver Cirrhosis / drug therapy*
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Transforming Growth Factor beta1 / metabolism
  • Up-Regulation

Substances

  • Actins
  • Diterpenes
  • HSP70 Heat-Shock Proteins
  • Tgfb1 protein, rat
  • Transforming Growth Factor beta1
  • smooth muscle actin, rat
  • Carbon Tetrachloride
  • Aspartate Aminotransferases
  • Alanine Transaminase
  • Bilirubin
  • Hydroxyproline
  • geranylgeranylacetone