Transforming growth factor beta in hepatitis C virus infection: in vivo and in vitro findings

J Gastroenterol Hepatol. 2003 Apr;18(4):393-403. doi: 10.1046/j.1440-1746.2003.02985.x.

Abstract

Background: Hepatitis C virus (HCV) is a leading cause of chronic liver disease (CLD) worldwide. The chronicity is a result of viral persistence and the ability of the virus to escape from the immune mechanisms of the host. Transforming growth factor (TGF)-beta is a cytokine thought to be responsible for viral persistence and liver fibrogenesis.

Methods: The present study examined the levels of TGF-beta messenger (m)RNA by reverse transcription polymerase chain reaction (RT-PCR) in 35 liver biopsies and HCV-transfected HepG2 cells.

Results: Transforming growth factor-beta mRNA was detected in nine liver biopsies from patients with chronic HCV infection, but was not detected in patients with non-HCV-related CLD or controls. On quantitation by semiquantitative PCR, TGF-beta mRNA levels ranged from 10-4.75 to 10-12.8 amol (10-7.46 +/- 3.771) in liver biopsies of HCV-related CLD. No significant difference in TGF-beta receptor levels was observed by RT-PCR in HCV- or non-HCV-related CLD by immunohistochemistry. To correlate these findings with in vitro experiments, levels of TGF-beta mRNA and its receptors were determined by RT-PCR in HepG2 cells transfected with HCV and hepatitis B virus (HBV) constructs, using mock-transfected cells as control. The TGF-beta protein levels were quantitated in these cell supernatants by enzyme immunoassay. The TGF-beta mRNA and protein levels were two logs and approximately 30 times higher in HCV-transfected HepG2 cells than in HBV- and mock-transfected cells, respectively. The TGF-beta receptors in HepG2 cells were also downregulated in HCV-transfected cells as compared with mock-transfected cells.

Conclusion: These observations suggest upregulation of TGF-beta in HCV infection and a probable role for TGF-beta in the pathogenesis of HCV-related CLD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Chronic Disease
  • Female
  • Hepacivirus / genetics*
  • Hepatitis C, Chronic / complications
  • Hepatitis C, Chronic / genetics*
  • Hepatitis C, Chronic / pathology
  • Hepatoblastoma / etiology
  • Hepatoblastoma / genetics*
  • Hepatoblastoma / pathology
  • Humans
  • In Vitro Techniques
  • Liver Neoplasms / etiology
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / pathology
  • Male
  • Middle Aged
  • RNA, Messenger / analysis*
  • RNA, Messenger / genetics*
  • Receptors, Transforming Growth Factor beta / analysis
  • Receptors, Transforming Growth Factor beta / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Risk Factors
  • Transforming Growth Factor beta / analysis*
  • Transforming Growth Factor beta / genetics*
  • Tumor Cells, Cultured

Substances

  • RNA, Messenger
  • Receptors, Transforming Growth Factor beta
  • Transforming Growth Factor beta