Hepatic HMOX1 expression positively correlates with Bach-1 and miR-122 in patients with HCV mono and HIV/HCV coinfection.

Elżbieta Jabłonowska,Anna Piekarska,Kamila Wójcik,Aleksandra Omulecka,Hanna Ćwiklińska,Bożena Szymańska

doi:10.1371/journal.pone.0095564

Abstract

AimTo analyze the expression of HMOX1 and miR-122 in liver biopsy samples obtained from HCV mono-and HIV/HCV co-infected patients in relation to selected clinical parameters, histological examination and IL-28B polymorphism as well as to determine whether HMOX1 expression is dependent on Bach-1.Materials and MethodsThe study group consisted of 90 patients with CHC: 69 with HCV mono and 21 with HIV/HCV co-infection. RT-PCR was used in the analysis of HMOX1, Bach-1 and miR-122 expression in liver biopsy samples and in the assessment of IL-28B single-nucleotide polymorphism C/T (rs12979860) in the blood. Moreover in liver biopsy samples an analysis of HO-1 and Bach-1 protein level by Western Blot was performed.ResultsHCV mono-infected patients, with lower grading score (G<2) and higher HCV viral load (>600000 IU/mL) demonstrated higher expression of HMOX1. In patients with HIV/HCV co-infection, the expression of HMOX1 was lower in patients with lower lymphocyte CD4 count and higher HIV viral load. IL28B polymorphism did not affect the expression of either HMOX1 or miR-122. Higher HMOX1 expression correlated with higher expression of Bach-1 (Spearman’s ρ = 0.586, p = 0.000001) and miR-122 (Spearman’s ρ = 0.270, p = 0.014059).ConclusionsHMOX1 and miR-122 play an important role in the pathogenesis of CHC in HCV mono-and HIV/HCV co-infected patients. Reduced expression of HMOX1 in patients with HIV/HCV co-infection may indicate a worse prognosis in this group. Our results do not support the importance of Bach-1 in repression of HMOX1 in patients with chronic hepatitis C.

Highlights

Hepatitis C virus infection (HCV) remains a worldwide health problem with about 3–4 million cases reported each year [1]
heme oxygenase-1 gene (HMOX1) and miR-122 play an important role in the pathogenesis of CHC in HCV mono-and HIV/HCV coinfected patients
Reduced expression of HMOX1 in patients with HIV/HCV co-infection may indicate a worse prognosis in this group

Summary

Introduction

Hepatitis C virus infection (HCV) remains a worldwide health problem with about 3–4 million cases reported each year [1]. 80% of patients become chronically infected after acute infection, 20% of whom progress to cirrhosis [2,3]. The annual rate of hepatocellular carcinoma (HCC) in cirrhosis patients is about 3–8% [4]. Reactive oxygen species (ROS) production can suppress HCV replication [7]. Excessive production may cause hepatocyte damage [8,9,10,11]. Antioxidant enzymes, such as Heme oxygenase-1 (HO-1), induced in response to ‘‘stressful stimuli’’, play a crucial role by suppressing inflammation and protecting against oxidative stress [12,13]

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