Hepatitis C virus infection stimulates transforming growth factor-β1 expression through up-regulating miR-192.
The objective of this study was to determine the molecular mechanisms underlying chronic liver injury and fibrosis caused by hepatitis C virus (HCV). This study revealed that miR-192 expreßsion was induced by HCV infection without affecting viral replication. However, viral-induced miR-192 up-regulated transforming growth factor-ß1 (TGF-ß1) expreßsion in liver cells at transcriptional level. TGF-ß1 stimulation by HCV-induced miR-192 was caused through ZEB1 down-regulation and TGF-ß1 increased miR-192 level via positive feedback pathway. Increase in miR-192 expreßsion by HCV infection was due to HCV core protein released and/or expressed by viral infection. TGF-ß1 promoter activity was also increased by HCV core protein in liver cells. Taken together, HCV infection resulted in increased TGF-ß1 transcription in hepatocytes through ZEB1 down-regulation by HCV core-mediated miR-192 stimulation. Importantly, miR-192 inhibition with anti-miR-192 rescued ZEB1 expression down-regulated by HCV infection, thus reducing the level of TGF-ß1 expression increased by HCV infection in hepatocytes. These results suggest a novel mechanism of HCV-mediated liver fibrogenesis with miR-192 being a potential molecular target to ameliorate viral pathogenesis.
['Kim|Ji Hyun|JH|', 'Lee|Chang Ho|CH|', 'Lee|Seong-Wook|SW|']
D016174:Hepacivirus D054884:Host-Pathogen Interactions D006801:Humans D008099:Liver D035683:MicroRNAs D011401:Promoter Regions, Genetic D053773:Transforming Growth Factor beta1 D015854:Up-Regulation D014758:Viral Core Proteins D000071799:Zinc Finger E-box-Binding Homeobox 1
hepatitis C Virus miR-192 ZEB1 TGF-β1 liver fibrosis