Effects and mechanisms of stilbene glucoside on the proliferation and collagen synthesis of cardiac fibroblasts stimulated by TGF-β1

The aim of this study was to investigate the effect of stilbene glucoside(2, 3, 4′, 5-tetrahydroxystilbene-2-O-β-D glucoside, TSG)on the cell proliferation and collagen synthesis in cultured neonatal rat cardiac fibroblasts(CFBs)stimulated by transforming growth factor-β1(TGF-β1)and to explore the underlying mechanisms. CFB were cultured from neonatal rats of 1-3 days and treated with TGF-β1. CFB proliferation was analyzed by 5-bromo-2-deoxyuridine(BrdU)incorporation assay. The synthesis of collagen was examined by measurement of the hydroxyproline concentration. Flow cytometry used to examined cell cycle of CFBs treated with TSG. The expressions of α-smooth muscle actin, proliferating cell nuclear antigen(PCNA), collagen Ⅰ, collagen Ⅲ, p-Smad2, Smad2, p-Smad3, Smad3, p-ERK, ERK, p-P38, P38, p-JNK, JNK were measured by Western blot. The results of the present study showed that TSG(0. 1-100 μmol/L)to exerted no significant cytotoxicity on the cells. Within a concentration coverage, TSG inhibited CFB proliferation and collagen synthesis with inhibition of cell cycle transition from G₀ /G₁ phase to S phase. Furthermore, TSG decreased the protein expressions of PCNA, α-smooth muscle actin, collagen Ⅰ, Collagen Ⅲ, p-Smad3, p-ERK and p-P38 stimulated by TGF-β1. Taken together, TSG significantly inhibited CFB proliferation and collagen synthesis stimulated by TGF-β1, though, at least in part, by suppression of Smad3, ERK and P38 activation.