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Antisense strategy against PDGF B-chain proves effective in preventing experimental liver fibrogenesis.

Authors: Borkham-Kamphorst, E  Stoll, D  Gressner, AM  Weiskirchen, R 
Citation: Borkham-Kamphorst E, etal., Biochem Biophys Res Commun. 2004 Aug 20;321(2):413-23.
Pubmed: (View Article at PubMed) PMID:15358192
DOI: Full-text: DOI:10.1016/j.bbrc.2004.06.153

Hepatic stellate cells (HSCs) and transdifferentiated myofibroblasts are the principal producers of excessive extracellular matrix in liver fibrosis and cirrhosis. Activation of HSC is regulated by several cytokines and growth factors, including platelet-derived growth factor B-chain (PDGF-B), a potent mitogen for HSC, and overexpressed during hepatic fibrogenesis. Previous studies showed that MAPK and phosphatidylinositol 3' kinase are key signaling pathways involved in PDGF-induced stimulation of HSC. Based on the involvement of PDGF-B in fibrogenesis, reducing ligand stimulation of proliferative cytokine- or growth factor receptors interfering with receptor signaling therefore presents an interesting strategy for hepatic fibrosis prevention or interruption. We therefore generated an adenoviral vector serotype 5 (Ad5) expressing an antisense mRNA of the PDGF B-chain (Ad5-CMV-asPDGF) for application in an experimentally induced liver fibrogenesis model. The transgene clearly showed the ability to down-regulate endogenous PDGF B-chain and PDGFRbeta mRNA in culture-activated HSC and rat livers. The asPDGF mRNA also attenuates experimental liver fibrogenesis indicated by reduced levels of alpha-SMA and collagen type I expression.

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RGD ID: 10449487
Created: 2016-01-06
Species: All species
Last Modified: 2016-01-06
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.