Heat shock protein 47 effects on hepatic stellate cell-associated receptors in hepatic fibrosis of Schistosoma japonicum-infected mice

Biol Chem. 2017 Nov 27;398(12):1357-1366. doi: 10.1515/hsz-2017-0177.

Abstract

The study aimed to explore the regulation of heat shock protein 47 (HSP47) on expressions of receptors associated with hepatic stellate cell (HSC) in liver fibrosis mouse models induced by Schistosoma japonicum (S. japonicum). Mouse fibroblasts (NIH/3T3) were transfected with HSP47 shRNA plasmid by lipofectamine transfection, and experimental fibrosis in HSCs was studied in S. japonicum mouse models treated with HSP47 shRNA in vivo. HSP47 expression was assessed using Western blot and real-time PCR. Flow cytometry was adopted to determine the expression of cell membrane receptors. HSP47-shRNA could markedly down-regulate the expression of collagen (Col1a1 and Col3a1). The expressions of HSP47, endothelin receptor A (ETAR) and endothelin receptor B (ETBR) significantly increased in the liver tissue of infected mice. However, the expressions of ETAR and HSP47 and ETBR remarkably decreased after the administration of HSP47 shRNA in vitro and in vivo. ETAR and ETBR levels were found to be positively correlated with HSP47 expression. HSP47 might exert influence on liver fibrosis via the regulation of ETAR and ETBR.

Keywords: Schistosoma japonicum; endothelin receptors; heat shock protein 47; hepatic fibrosis.

MeSH terms

  • Animals
  • Cells, Cultured
  • Disease Models, Animal
  • Female
  • HSP47 Heat-Shock Proteins / metabolism*
  • Hepatic Stellate Cells / metabolism*
  • Hepatic Stellate Cells / pathology
  • Liver Cirrhosis / metabolism*
  • Liver Cirrhosis / pathology
  • Mice
  • Mice, Inbred BALB C
  • NIH 3T3 Cells
  • Receptor, Endothelin A / metabolism*
  • Receptor, Endothelin B / metabolism*
  • Schistosoma japonicum / metabolism*
  • Schistosoma japonicum / parasitology

Substances

  • HSP47 Heat-Shock Proteins
  • Receptor, Endothelin A
  • Receptor, Endothelin B
  • Serpinh1 protein, mouse