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- W2024443323 abstract "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 downregulate endogenous PDGF B-chain and PDGFRβ mRNA in culture-activated HSC and rat livers. The asPDGF mRNA also attenuates experimental liver fibrogenesis indicated by reduced levels of α-SMA and collagen type I expression." @default.
- W2024443323 created "2016-06-24" @default.
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- W2024443323 date "2004-08-01" @default.
- W2024443323 modified "2023-10-16" @default.
- W2024443323 title "Antisense strategy against PDGF B-chain proves effective in preventing experimental liver fibrogenesis" @default.
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- W2024443323 doi "https://doi.org/10.1016/j.bbrc.2004.06.153" @default.
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