We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Hepatitis C virus infection and hepatic stellate cell activation downregulate miR-29: miR-29 overexpression reduces hepatitis C viral abundance in culture.
- Authors
Bandyopadhyay S; Friedman RC; Marquez RT; Keck K; Kong B; Icardi MS; Brown KE; Burge CB; Schmidt WN; Wang Y; McCaffrey AP; Bandyopadhyay, Sarmistha; Friedman, Robin C; Marquez, Rebecca T; Keck, Kathy; Kong, Benjamin; Icardi, Michael S; Brown, Kyle E; Burge, Christopher B; Schmidt, Warren N
- Abstract
<bold>Background: </bold>Chronic hepatitis C virus (HCV)-induced liver fibrosis involves upregulation of transforming growth factor (TGF)-β and subsequent hepatic stellate cell (HSC) activation. MicroRNAs (miRNAs) regulate HCV infection and HSC activation.<bold>Methods: </bold>TaqMan miRNA profiling identified 12 miRNA families differentially expressed between chronically HCV-infected human livers and uninfected controls. To identify pathways affected by miRNAs, we developed a new algorithm (pathway analysis of conserved targets), based on the probability of conserved targeting.<bold>Results: </bold>This analysis suggested a role for miR-29 during HCV infection. Of interest, miR-29 was downregulated in most HCV-infected patients. miR-29 regulates expression of extracellular matrix proteins. In culture, HCV infection downregulated miR-29, and miR-29 overexpression reduced HCV RNA abundance. miR-29 also appears to play a role in HSCs. Hepatocytes and HSCs contribute similar amounts of miR-29 to whole liver. Both activation of primary HSCs and TGF-β treatment of immortalized HSCs downregulated miR-29. miR-29 overexpression in LX-2 cells decreased collagen expression and modestly decreased proliferation. miR-29 downregulation by HCV may derepress extracellular matrix synthesis during HSC activation.<bold>Conclusions: </bold>HCV infection downregulates miR-29 in hepatocytes and may potentiate collagen synthesis by reducing miR-29 levels in activated HSCs. Treatment with miR-29 mimics in vivo might inhibit HCV while reducing fibrosis.
- Subjects
CELL metabolism; RNA metabolism; RNA analysis; ALGORITHMS; BIOCHEMISTRY; COLLAGEN; EPITHELIAL cells; HEPATITIS viruses; LIVER; PHENOMENOLOGY; POLYMERASE chain reaction; RESEARCH funding; REVERSE transcriptase polymerase chain reaction; CHRONIC hepatitis C
- Publication
Journal of Infectious Diseases, 2011, Vol 203, Issue 12, p1753
- ISSN
0022-1899
- Publication type
journal article
- DOI
10.1093/infdis/jir186