NGF and P75NTR Gene Expression Is Associated with the Hepatic Fibrosis Stage Due to Viral and Non-Viral Causes

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.ConclusionOur 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.

Intrahepatic mRNA Expression of FAS, FASL, and FOXP3 Genes Is Associated with the Pathophysiology of Chronic HCV Infection

“…Previous study from our group has reported the association between the NGF and P75 NRT gene expressions and the liver fibrosis stages due to viral and non-viral causes [ 8 ]. Into this perspective, the present work aims to continue to investigate the factors associated with fibrosis by quantifying expression of the Fas , FasL , and FOXP3 genes in liver biopsy specimens obtained from patients with viral (HBV and HCV) and non-viral hepatic disease (NVHD) chronic hepatitis and correlate their possible roles in the pathogenesis and clinical presentation of these infections and in the various stages of fibrosis and hepatic inflammatory activity.…”

NGF (−198C > T, Ala35Val) and p75NTR (Ser205Leu) gene mutations are associated with liver function in different histopathological profiles of the patients with chronic viral hepatitis in the Brazilian Amazon

“…The paracrine loop between the neurotrophins produced by hepatocytes and the p75 NTR receptor expressed in HSCs, which, on the one hand, stimulates hepatocyte proliferation and, on the other hand, blocks and regulates this phenomenon (Amoras et al, 2015), was not the concept adopted in the present study. Based on the evaluation of polymorphic variants well established in the literature, we suggest that NGF has a regulatory role in maintenance of hepatocyte integrity, leading to reducing liver enzyme levels and increase of the viral load.…”

“…NGF and p75 NTR are naturally expressed in healthy liver tissue and under conditions of tissue damage (Passino et al, 2007), and their physiological roles are related to inflammation and the progression of liver fibrosis (Amoras et al, 2015). Thus, it is important to evaluate the influence of genetic variations on these factors as aspects linked to the evolution of liver damage in patients with liver disease.…”

“…Considering that the variant alters NGF gene expression (Akkad et al, 2008, Hahn et al, 2011, in the context of viral liver diseases, it is proposed that negative gene maintenance be detrimental to organ tissue integrity in the most advanced aggression profiles, which underscores the importance of NGF in controlling liver damage. In fact, in experimentally intoxicated mice, it has been shown that NGF expression by hepatocytes is directly regulated in areas of tissue regeneration during aggression (Oakley et al, 2003) (which in humans is a characteristic maintained in the advanced fibrosis stage) being pointed as a potential determinant in the resolution of the fibrotic response (Amoras et al, 2015).…”

“…With the improvement in molecular detection techniques, the expression of NGF and p75 NTR in nonneuronal cell lines could be observed. In the hepatic microenvironment, NGF is expressed in damaged hepatocytes, exerts an apoptotic effect on fibrogenic cells via p75 NTR (Oakley et al, 2003) and upregulates hepatoprotective components in cholestatic liver tissue (Tsai et al, 2018), suggesting that neurotrophins participate in the control of liver injury, as observed in cirrhotic tissues (Cassiman et al, 2001); however, other conclusions have been inferred when analyzing different neurotrophin receptors (Rasi et al, 2007), ligands (Kendall et al, 2009) and histological stages of the liver (Amoras et al, 2015).…”