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Hepatitis C Virus Infection is Highly Correlated with Hepatocellular Apoptosis and Transforming Growth Factor‐β1 MRNA Expression in Patients with Chronic Hepatitis C
Author(s) -
Manabe N,
Goto Y,
Anan S,
Suzuki T,
Matsuura Y,
Miyamura T
Publication year - 2005
Publication title -
wound repair and regeneration
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.847
H-Index - 109
eISSN - 1524-475X
pISSN - 1067-1927
DOI - 10.1111/j.1067-1927.2005.130117r.x
Subject(s) - in situ hybridization , tunel assay , proliferating cell nuclear antigen , apoptosis , hepatocyte , hepatitis c virus , biology , microbiology and biotechnology , hepatocellular carcinoma , hepatitis c , immunohistochemistry , hepatitis , virus , messenger rna , virology , immunology , cancer research , gene , biochemistry , in vitro
To determine whether hepatocellular apoptosis is involved in chronic liver injury in patients with chronic hepatitis C, the correlations among the rate of hepatocellular apoptosis, the rate of hepatocytes infected with hepatitis C virus (HCV) and TGF‐β1 mRNA expression, were histologically examined. HCV was visualized by in situ PCR technique. Apoptotic hepatocytes were determined by TUNEL technique. TGF‐β1 mRNA expression was quantified by Northern blotting analysis, and visualized by in situ hybridization. Fas‐antigen and proliferating cell nuclear antigen (PCNA) on hepatocytes, and α‐smooth muscle actin (αSMA) and desmin were evaluated by immunohistochemistry. In the areas of inflammation, TUNEL‐positive apoptotic hepatocytes and PCNA‐positive hepatocytes were occasionally observed around HCV‐positive hepatocyte. TGF‐β1 mRNA‐positive myofibroblast‐like Ito cells (double‐positive for αSMA and desmin) were also observed near the HCV‐positive hepatocytes. Fas‐antigen was detected on the surface of most hepatocytes in all lobules. A high correlation was found between the rate of HCV positive hepatocytes and that of apoptotic hepatocytes (r = 0.81, P < 0.05). The increase in number of HCV‐positive hepatocytes was linked to the increases in TGF‐β1 mRNA level (r = 0.79, P < 0.05) and number of TGF‐β1 mRNA‐positive Ito cells (r = 0.74, P < 0.05). These findings confirmed that the increase in HCV‐infected hepatocytes is related to the increase of hepatocellular apoptosis and the increase of TGF‐β1 mRNA in the liver of hepatitis C patients. TGF‐β1 plays an important role in apoptosis of hepatocytes infected with HCV.