期刊
JOURNAL OF INFECTIOUS DISEASES
卷 203, 期 12, 页码 1753-1762出版社
OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jir186
关键词
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资金
- University of Iowa, College of Medicine
- University of Iowa, Levitt Center for Viral Pathogenesis
- University of Iowa
- National Institute of Allergy and Infectious Diseases [T32AI007533]
- Veterans Administration
- National Institutes of Health [R21 DK068453-01A1]
- University of Iowa Carver Trust Foundation
- Department of Energy
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-beta 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.
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