Journal article
Correlation between microRNA expression levels and clinical parameters associated with chronic hepatitis C viral infection in humans
Laboratory investigation, Vol.90(12), pp.1727-1736
12/2010
DOI: 10.1038/labinvest.2010.126
PMID: 20625373
Abstract
MicroRNAs (miRNAs) are small RNAs that regulate gene expression pathways. Previous studies have shown interactions between hepatitis C virus (HCV) and host miRNAs. We measured miR-122 and miR-21 levels in HCV-infected human liver biopsies relative to uninfected human livers and correlated these with clinical patient data. miR-122 is required for HCV replication in vitro, and miR-21 is involved in cellular proliferation and tumorigenesis. We found that miR-21 expression correlated with viral load, fibrosis and serum liver transaminase levels. miR-122 expression inversely correlated with fibrosis, liver transaminase levels and patient age. miR-21 was induced ∼twofold, and miR-122 was downregulated on infection of cultured cells with the HCV J6/JFH infectious clone, thus establishing a link to HCV. To further examine the relationship between fibrosis and the levels of miR-21 and miR-122, we measured their expression levels in a mouse carbon tetrachloride fibrosis model. As in the HCV-infected patient samples, fibrotic stage positively correlated with miR-21 and negatively correlated with miR-122 levels. Transforming growth factor β (TGF-β) is a critical mediator of fibrogenesis. We identified SMAD7 as a novel miR-21 target. SMAD7 is a negative regulator of TGF-β signaling, and its expression is induced by TGF-β. To confirm the relationship between miR-21 and the TGF-β signaling pathway, we measured the effect of miR-21 on a TGF-β-responsive reporter. We found that miR-21 enhanced TGF-β signaling, further supporting a relationship between miR-21 and fibrosis. We suggest a model in which miR-21 targeting of SMAD7 could increase TGF-β signaling, leading to increased fibrogenesis.
Details
- Title: Subtitle
- Correlation between microRNA expression levels and clinical parameters associated with chronic hepatitis C viral infection in humans
- Creators
- Rebecca T Marquez - Department of Internal Medicine, University of Iowa School of Medicine, University of Iowa, Iowa City, IA 52242, USASarmistha BandyopadhyayErik B WendlandtKathy KeckBrandon A HofferMichael S IcardiRandolph N ChristensenWarren N SchmidtAnton P McCaffrey
- Resource Type
- Journal article
- Publication Details
- Laboratory investigation, Vol.90(12), pp.1727-1736
- Publisher
- United States
- DOI
- 10.1038/labinvest.2010.126
- PMID
- 20625373
- ISSN
- 0023-6837
- eISSN
- 1530-0307
- Grant note
- I01 BX000159 / BLRD VA R21 DK068453-01A1 / NIDDK NIH HHS T32AI007533 / NIAID NIH HHS
- Language
- English
- Date published
- 12/2010
- Academic Unit
- Gastroenterology and Hepatology; Pathology; Internal Medicine
- Record Identifier
- 9984046929102771
Metrics
12 Record Views