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- Title
Targeted inhibition of platelet-derived growth factor receptor-β subunit in hepatic stellate cells ameliorates hepatic fibrosis in rats.
- Authors
Chen, S-W; Chen, Y-X; Zhang, X-R; Qian, H; Chen, W-Z; Xie, W-F
- Abstract
The activation of hepatic stellate cells (HSCs) is the key event of the pathogenesis of hepatic fibrosis. Platelet-derived growth factor (PDGF) is the most potent mitogen for HSCs, and PDGF receptor-β subunit (PDGFR-β) is required for the proliferation of HSCs induced by PDGF. In this study, a high gene-silencing-efficacy PDGFR-β small interference RNA (siRNA) was synthesized that could suppress the PDGFR-β expression and inhibit the activation and proliferation but could not induce the apoptosis of HSCs in vitro. To avoid the side effect of nonspecific interference of PDGFR-β, we constructed an HSCs-specific short hairpin RNA (shRNA) expression plasmid in which PDGFR-β shRNA was driven by a glial fibrillary acidic protein (GFAP) promoter. The double-staining immunofluorescence examination indicated that GFAP promoter could target the transgene expression into HSCs in carbon tetrachloride induced acute injured rat's liver and bile duct ligation (BDL)-induced chronic injured rat's liver. Furthermore, HSCs-specific PDGFR-β shRNA could relieve liver injury and hepatic fibrosis in the rat's model induced by BDL. This study demonstrates that PDGFR-β siRNA may be presented as an antifibrogenic agent. The application of HSCs-specific RNA interference induced by the GFAP promoter might supply a new powerful tool for cell-specific gene therapy of hepatic fibrogenesis.Gene Therapy (2008) 15, 1424–1435; doi:10.1038/gt.2008.93; published online 29 May 2008
- Subjects
FIBROSIS; LIVER diseases; LIVER cells; GROWTH factors; RNA; GENE therapy; RATS
- Publication
Gene Therapy, 2008, Vol 15, Issue 21, p1424
- ISSN
0969-7128
- Publication type
Article
- DOI
10.1038/gt.2008.93