Hosui Atsushi, Takehara Tetsuo, Ohkawa Kazuyoshi, Kanazawa Yoshiyuki, Tatsumi Tomohide, Yamaguchi Shinjiro, Sakamori Ryotaro, Hiramatsu Naoki, Kanto Tatsuya, Hayashi Norio
Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita 565-0871, Japan.
Biochem Biophys Res Commun. 2006 Aug 11;346(4):1125-30. doi: 10.1016/j.bbrc.2006.05.114. Epub 2006 May 26.
The influence of hepatitis C virus (HCV) protein(s) on cellular differentiation remains to be clarified. Using murine normal liver epithelial cells, we investigated whether HCV core protein affects differentiation into hepatocytes. Mock and HCV core-expressing cells were stimulated with oncostatin M (OSM) and dexamethasone, and the degree of differentiation was evaluated by measuring the expression of albumin and tyrosine aminotransferase (TAT). Lower amounts after stimulation were found in HCV core-expressing cells than in mock cells. Phosphorylation of the signal transducer and activator transcription factor 3 (STAT3) was prevented by the HCV core under OSM stimulation. Reporter gene assay revealed that the HCV core/Janus kinase (JAK) interaction directly suppressed the OSM-dependent JAK-STAT signal transduction. Furthermore, expression of OSM receptor beta (OSMRbeta) after stimulation was prevented by the HCV core. In conclusion, the HCV core may suppress differentiation into hepatocytes via inhibition of the JAK-STAT pathway and OSMRbeta expression.
丙型肝炎病毒（HCV）蛋白对细胞分化的影响仍有待阐明。我们使用小鼠正常肝上皮细胞，研究了HCV核心蛋白是否会影响向肝细胞的分化。用制瘤素M（OSM）和地塞米松刺激空载体对照细胞和表达HCV核心蛋白的细胞，并通过测量白蛋白和酪氨酸转氨酶（TAT）的表达来评估分化程度。结果发现，与空载体对照细胞相比，表达HCV核心蛋白的细胞在刺激后表达量更低。在OSM刺激下，HCV核心蛋白可阻止信号转导和转录激活因子3（STAT3）的磷酸化。报告基因分析表明，HCV核心蛋白与Janus激酶（JAK）的相互作用直接抑制了OSM依赖的JAK-STAT信号转导。此外，HCV核心蛋白可阻止刺激后OSM受体β（OSMRβ）的表达。总之，HCV核心蛋白可能通过抑制JAK-STAT途径以及OSMRβ的表达来抑制向肝细胞的分化。
