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由于病毒和非病毒原因,NGF和P75NTR基因表达与肝纤维化阶段相关。

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

作者信息

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

机构信息

Laboratory of Virology, Institute of Biological Sciences, Federal University of Pará (Universidade Federal do Pará-UFPA), Belém, Pará, Brazil.

João de Barros Barreto Hospital, Federal University of Pará (Universidade Federal do Pará-UFPA), Belém, Pará, Brazil.

出版信息

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.

摘要

本研究评估了神经生长因子(NGF)和p75神经营养因子受体(p75NTR)在人类肝脏疾病不同组织学阶段的相对mRNA表达水平。从乙型肝炎病毒患者(n = 6)、丙型肝炎病毒患者(n = 28)、非病毒性肝炎患者(n = 9)以及作为对照(CT)的标准组织学肝脏患者(n = 8)获取的51份肝活检标本接受了qPCR和组织病理学检查。我们的数据显示,三个患者组与对照组之间NGF表达水平存在显著差异。丙型肝炎病毒组和非病毒性肝炎组中的p75NTR表达水平高于乙型肝炎病毒组和对照组。在肝硬化病例中,观察到p75NTR mRNA表达较高,而在肝纤维化患者中NGF表达水平较高。在F1肝纤维化阶段NGF表达较低,与纤维化程度增加相比,p75NTR受体表达持续且成比例增加,在纤维化3期和4期的肝脏中显著更高。相对于炎症活动阶段,肝脏中NGF和p75NTR水平分别降低和升高。在轻度至中度纤维化的肝脏中观察到p75NTR与NGF基因表达呈正相关,但在重度纤维化和肝硬化病例中未观察到。结论:我们的结果表明,慢性肝病进程可由NGF和p75NTR调节,它们通过减少或抑制肝细胞再生和增殖发挥作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9bbd/4376854/174702610b2a/pone.0121754.g001.jpg

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