Abstract
Background/Aims: Platelet-derived growth factor (PDGF) is implicated in the activation of hepatic stellate cells (HSCs), the key cell population in liver fibrogenesis. We depleted the expression of PDGF receptor-ß (PDGFR-ß) and assessed the role in the activation of HSCs. Methods: We used the wildtype and mutant mice whose PDGFR-ß gene was flanked by two loxP sequences, and isolated/cultured HSCs from these two mice, respectively. These cells were infected with Cre recombinase-expressing adenovirus. Results: After Cre-adenovirus infection, PDGFR-ß expression was depleted in HSCs from mutant mice (PDGFR-ßΔ/Δ), but was preserved in those from wild-type. We detected the expression of PDGFR-α and PDGF-A, -B, -C, and -D at similar levels between WT and PDGFR-ßΔ/Δ. BrdU-incorporation in PDGFR-ßΔ/Δ was suppressed in serum-starved/non-stimulated and PDGF-BB stimulated conditions, respectively. PDGF-BB-induced wound closure was apparently delayed in PDGFR-ßΔ/Δ. α1 (I) collagen mRNA was low in PDGFR-ßΔ/Δ, sparing α-smooth muscle actin mRNA at WT levels. Conclusions: The HSCs expressed two types of PDGFR; however, PDGFR-ß was distinctively relevant in the activation of HSCs by mediating both endogenous and exogenous PDGF signals.
