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Hepatitis C virus infection stimulates transforming growth factor-β1 expression through up-regulating miR-192

  • Virology
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Abstract

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.

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  1. Department of Molecular Biology, Research Institute of Advanced Omics, Dankook University, Yongin, 16890, Republic of Korea

    Ji Hyun Kim, Chang Ho Lee & Seong-Wook Lee

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  1. Ji Hyun Kim
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  2. Chang Ho Lee
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Correspondence to Seong-Wook Lee.

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Kim, J.H., Lee, C.H. & Lee, SW. Hepatitis C virus infection stimulates transforming growth factor-β1 expression through up-regulating miR-192. J Microbiol. 54, 520–526 (2016). https://doi.org/10.1007/s12275-016-6240-3

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