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

Ednelza Da Silva Graça Amoras,Marialva Tereza Ferreira De Araújo,Bárbara Brasil Santana,Ricardo Ishak,Samara Tatielle Monteiro Gomes,Antonio Carlos Rosário Vallinoto,Felipe Bonfim Freitas,Simone Regina Souza Da Silva Conde,Geraldo Ishak,Marluísa De Oliveira Guimarães Ishak,Sâmia Demachki,Matias A Avila

doi:10.1371/journal.pone.0121754

Ednelza Da Silva Graça Amoras, Marialva Tereza Ferreira De Araújo + Show 10 more

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https://doi.org/10.1371/journal.pone.0121754

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Journal: PloS one	Publication Date: Mar 27, 2015
Citations: 12	License type: CC BY 4.0

Affiliation: Universidade Federal do Pará

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.

Highlights

Viral hepatitis is one of the great pandemics of our time
Our results demonstrate that the course of chronic liver disease can be regulated by nerve growth factor (NGF) and p75 neurothrophin receptor (p75NTR), which function by decreasing or inhibiting hepatocyte regeneration and proliferation
Mean ALT levels were higher in thegroups of patients with hepatitis C virus (HCV) (89 IU/L) and NVH (97 IU/L); the same was observed for gamma-glutamyl transferase (GGT) (78 IU/L and 179 IU/L, respectively)

Summary

Introduction

Viral hepatitis is one of the great pandemics of our time. Hepatitis B virus (HBV) and hepatitis C virus (HCV) are responsible for the vast majority of chronic liver diseases worldwide; they are important public health problems [1]. As a consequence of chronic liver injury, quiescent hepatic stellate cells (HSCs), which store fat and vitamin A, undergo differentiation to an activated myofibroblastic phenotype under the action of pro-inflammatory cytokines, increasing synthesis levels of extracellular matrix components (i.e., collagens, elastin, proteoglycans and constituent proteins) [5,6]. This HSC activation is accompanied by a reorganization and expression of cytoskeletal proteins, such as αsmooth muscle actin (α-SMA), that acquire pro-fibrogenic properties [7]. The excessive deposition of extracellular matrix is the result of an imbalance between fibrogenesis and fibrolysis in the liver, and the proportion of deposited extracellular matrix becomes greater than the amount removed, especially collagen types I and II, proteoglycans, and glycoproteins [7]

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