title: Hepatitis C virus infection and hepatic stellate cell activation downregulate miR-29: miR-29 overexpression reduces hepatitis C viral abundance in culture.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: University of Iowa School of Medicine, Department of Internal Medicine, University of Iowa, 3166 MERF, Iowa City, IA 52242, USA.
authors: Sarmistha
authors: S
authors: Bandyopadhyay
authors: Robin C
authors: RC
authors: Friedman
authors: Rebecca T
authors: RT
authors: Marquez
authors: Kathy
authors: K
authors: Keck
authors: Benjamin
authors: B
authors: Kong
authors: Michael S
authors: MS
authors: Icardi
authors: Kyle E
authors: KE
authors: Brown
authors: Christopher B
authors: CB
authors: Burge
authors: Warren N
authors: WN
authors: Schmidt
authors: Yulei
authors: Y
authors: Wang
authors: Anton P
authors: AP
authors: McCaffrey
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