NGF and P75NTR gene expression is associated with the hepatic fibrosis stage due to viral and non-viral causes

PLoS One. 2015 Mar 27;10(3):e0121754. doi: 10.1371/journal.pone.0121754. eCollection 2015.

Abstract

This study evaluated the relative mRNA expression levels of nerve growth factor (NGF) and the p75 neurothrophin receptor (p75NTR) in different histological stages of human liver disease. Fifty-one liver biopsy specimens obtained from patients with hepatitis B virus (n = 6), hepatitis C virus (n = 28), and non-viral hepatitis--(n = 9) and standard histological liver (n = 8) as controls (CT) were subjected to qPCR and histopathological exams. Our data revealed a significant difference in the NGF expression levels between the three patient groups and the Control group. p75NTR expression levels in the HCV and NVH groups were higher than those observed in the HBV and Control groups. In cases of liver cirrhosis, higher p75NTR mRNA expression was observed, whereas NGF was expressed at higher levels in patients with hepatic fibrosis. NGF expression was lower in the F1 liver fibrosis stage, and p75NTR receptor expression continuously and proportionately increased compared to the increase in the degree of fibrosis and was significantly higher in livers in fibrosis stages 3 and 4. The hepatic levels of NGF and p75NTR were decreased and increased, respectively, relative to the stage of inflammatory activity. A positive correlation between p75NTR and NGF gene expression was observed in livers with mild to moderate fibrosis, though not in cases of severe fibrosis and cirrhosis. Conclusion: Our results demonstrate that the course of chronic liver disease can be regulated by NGF and p75NTR, which function by decreasing or inhibiting hepatocyte regeneration and proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Female
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Hepatitis B / genetics
  • Hepatitis B / pathology
  • Hepatitis C / genetics
  • Hepatitis C / pathology
  • Humans
  • Liver / pathology
  • Liver / virology
  • Liver Cirrhosis / genetics*
  • Liver Cirrhosis / pathology*
  • Liver Cirrhosis / virology
  • Male
  • Nerve Growth Factor / genetics*
  • Nerve Tissue Proteins / genetics*
  • Receptors, Nerve Growth Factor / genetics*
  • Up-Regulation

Substances

  • NGF protein, human
  • NGFR protein, human
  • Nerve Tissue Proteins
  • Receptors, Nerve Growth Factor
  • Nerve Growth Factor

Grants and funding

This study was funded by the National Council for Scientific and Technological Development (Conselho Nacional de Desenvolvimento Científico e Tecnológico—CNPq) and by the Dean of Research and Graduate Studies Office (Pró-Reitoria de Pesquisa e Pós-Graduação—PROPESP/UFPA). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.