Scavenging endogenous PDGF B-chain by adenovirus-mediated PDGFbetaR-Fc gene transfer potentially inhibits HSC activation and attenuates liver fibrosis

Platelet-derived growth factor (PDGF), especially its B chain, has been implicated in the pathogenesis of proliferative disorders such as malignancies, atherosclerosis, and fibrotic conditions. We constructed a replication-deficient recombinant adenovirus containing the gene encoding an extracellular domain of rat PDGFbeta receptor (PDGFbetaR) fused with human IgG-Fc. The adenoviral PDGFbetaR-Fc construct was transduced into culture-activated rat hepatic stellate cells, resulting in inhibition of PDGF induced tyrosine phosphorylation of the endogenous PDGFbeta receptor, phosphorylation of extracellular signal-re…