Abstract: Objective To investigate the effect of TGF-β1 on Shh signaling pathway during the transformation of meningeal fibroblasts into myofibroblasts. Methods Primary meningeal fibroblasts were isolated from neonatal (24 h) SD rats and purified using type Ⅳ collagenase. The isolated cells were treated with 10 ng/mL TGF-β1 alone or in combination with 20 μmol/L SB-431542 (a TGF-β1 receptor inhibitor) for 72 h, and the changes in proliferation and migration abilities of the fibroblasts were assessed with CCK-8 assay and cell scratch test. The expression of fibronectin (Fn) was detected with immunofluorescence assay, and Western blotting was performed to examine the expressions of Fn, α-SMA and Shh protein in the cells; the expression of Shh mRNA was detected with real-time fluorescence quantitative PCR. Results TGF-β1 treatment obviously enhanced the proliferation and migration of primary meningeal fibroblasts (P<0.05), and promoted the transformation of meningeal fibroblasts into myofibroblasts and the secretion of Fn (P<0.05). TGF-β1 treatment also upregulated the expression of Shh at both protein and mRNA levels (P<0.05). Treatment with SB-431542 partially blocked the effect of TGF-β1 on the transformation of meningeal fibroblasts (P<0.05). Conclusion TGF-β1 can induce the transformation of meningeal fibroblasts into myofibroblasts by up-regulating Shh expression in Sonic Hedgehog signaling pathway.

Key words: transforming growth factor-β1; fibroblasts; myofibroblasts; Shh signaling