Title |
Hepatitis C virus infection stimulates transforming growth factor-β1 expression through up-regulating miR-192 |
Author |
Ji Hyun Kim, Chang Ho Lee, and Seong-Wook Lee* |
Address |
Department of Molecular Biology, Research Institute of Advanced Omics, Dankook University, Yongin 16890, Republic of Korea |
Bibliography |
Journal of Microbiology, 54(7),520-526, 2016,
|
DOI |
10.1007/s12275-016-6240-3
|
Key Words |
hepatitis C Virus, liver fibrosis, miR-192, TGF-β1,ZEB1 |
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 expression was induced by HCV infection without
affecting viral replication. However, viral-induced miR-192
up-regulated transforming growth factor-β1 (TGF-β1) expression
in liver cells at transcriptional level. TGF-β1 stimulation
by HCV-induced miR-192 was caused through ZEB1
down-regulation and TGF-β1 increased miR-192 level via
positive feedback pathway. Increase in miR-192 expression
by HCV infection was due to HCV core protein released
and/or expressed by viral infection. TGF-β1 promoter activity
was also increased by HCV core protein in liver cells.
Taken together, HCV infection resulted in increased TGF-β1
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-β1 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. |