Journal article
Hepatitis C Virus Infection and Hepatic Stellate Cell Activation Downregulate miR-29: miR-29 Overexpression Reduces Hepatitis C Viral Abundance in Culture
The Journal of infectious diseases, Vol.203(12), pp.1753-1762
06/15/2011
DOI: 10.1093/infdis/jir186
PMCID: PMC3143452
PMID: 21606534
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.
Details
- Title: Subtitle
- Hepatitis C Virus Infection and Hepatic Stellate Cell Activation Downregulate miR-29: miR-29 Overexpression Reduces Hepatitis C Viral Abundance in Culture
- Creators
- Sarmistha Bandyopadhyay - University of Iowa School of Medicine, Department of Internal Medicine, University of IowaRobin C Friedman - Department of Biology, Massachusetts Institute of Technology, CambridgeRebecca T Marquez - Department of Pharmacology, University of Kansas Medical Center, Kansas CityKathy Keck - University of Iowa School of Medicine, Department of Internal Medicine, University of IowaBenjamin Kong - Life Technologies, Foster City, CaliforniaMichael S Icardi - Department of Pathology and Research ServiceKyle E Brown - Department of Iowa City Veterans Administration Medical Center, Division of Gastroenterology-Hepatology and Program in Free Radical and Radiation Biology, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa CityChristopher B Burge - Department of Biology, Massachusetts Institute of Technology, CambridgeWarren N Schmidt - Department of Internal Medicine and Research Service, Veterans Administration Medical Center, 200 Hawkins DriveYulei Wang - Life Technologies, Foster City, CaliforniaAnton P McCaffrey - University of Iowa School of Medicine, Department of Internal Medicine, University of Iowa
- Resource Type
- Journal article
- Publication Details
- The Journal of infectious diseases, Vol.203(12), pp.1753-1762
- Publisher
- Oxford University Press
- DOI
- 10.1093/infdis/jir186
- PMID
- 21606534
- PMCID
- PMC3143452
- ISSN
- 0022-1899
- eISSN
- 1537-6613
- Language
- English
- Date published
- 06/15/2011
- Academic Unit
- Gastroenterology and Hepatology; Pathology; Radiation Oncology; Internal Medicine
- Record Identifier
- 9984046808202771
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