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

Abstract

Aim: To 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 methods: The 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.

Results: HCV 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).

Conclusions: HMOX1 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.

Figure 1. Presence of HO-1 protein levels for representative patients (Western Blot analysis).

Figure 2. HO-1 protein levels in selected patients with HIV/HCV co-infection (Western Blot analysis).

Figure 3. Correlation between the expression of HMOX1 and Bach-1. Gene expression was analyzed by relative quantitative (RQ) real-time PCR. mRNA levels were normalized to ACTB. Higher HMOX1 expression correlated with a higher expression of Bach-1 (Spearman’s rank correlation coefficient; ρ = 0.586, p = 0.000001).

Figure 4. Positive correlation between HO-1 and Bach-1 protein level (Western Blot analysis).

Figure 5. Correlation between the expression of HMOX1 and miR-122. Gene expression was analyzed by relative quantitative (RQ) real-time PCR. mRNA levels were normalized to ACTB for HMOX1 and to RNU24 for miR-122. Higher HMOX1 expression correlated with higher expression of miR-122. (Spearman’s rank correlation coefficient; ρ = 0.270, p = 0.014059).

Figure 6. Correlation between ALT activity (U/L) and miR-122 expression. Gene expression was analyzed by relative quantitative (RQ) real-time PCR. mRNA levels were normalized to RNU24 for miR-122. Higher ALT activity correlated with a lower expression of miR-122 (Spearman’s rank correlation coefficient; ρ = −0.336, p = 0.001196).