Department of Dermatology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi 371-8511, Japan.
Eur J Dermatol. 2012 Jan-Feb;22(1):46-53. doi: 10.1684/ejd.2011.1582.
Although recent clinical reports have indicated that recombinant basic fibroblast growth factor (bFGF) promotes scarless wound healing, the mechanism remains unclear. The present study was carried out to elucidate the mechanisms. The protein levels of cellular α-smooth muscle actin increased at 2-4 days after TGFβ treatment alone and at 4 to 6 days after a costimulation of bFGF and TGFβ. A spontaneous contraction of stressed myofibroblast-collagen matrix was cancelled by bFGF, which was restored under the presence of C3 exotransferase or Y27632. bFGF stimulation of myofibroblasts as well as fibroblasts elicited a transient Rac and Rho activation. bFGF promoted apoptosis of the myofibroblasts but not of the fibroblasts, even in the presence of two different inhibitors, either LY294002 or an Akt inhibitor. The present study suggests that the phosphatidylinositol-3-kinase to Akt as well as the Rho to Rho kinase signaling pathway is involved in bFGF-promoted myofibroblast apoptosis, and bFGF can promote the scarless wound healing upon the induction of apoptosis of myofibroblasts, but not fibroblasts.
尽管最近的临床报告表明，重组碱性成纤维细胞生长因子（bFGF）可促进无瘢痕愈合，但具体机制尚不清楚。本研究旨在阐明其机制。TGFβ 单独处理 2-4 天后，细胞 α-平滑肌肌动蛋白的蛋白水平增加，bFGF 和 TGFβ 共同刺激 4-6 天后增加。bFGF 可取消应激成肌纤维细胞-胶原基质的自发收缩，在 C3 外转酶或 Y27632 的存在下恢复收缩。bFGF 刺激成肌纤维细胞和纤维母细胞可引发 Rac 和 Rho 的短暂激活。bFGF 促进成肌纤维细胞的凋亡，但不促进纤维母细胞的凋亡，即使存在两种不同的抑制剂（LY294002 或 Akt 抑制剂）也是如此。本研究表明，PI3K-Akt 以及 Rho 至 Rho 激酶信号通路参与了 bFGF 促进的成肌纤维细胞凋亡，bFGF 可通过诱导成肌纤维细胞凋亡来促进无瘢痕愈合，但不会诱导纤维母细胞凋亡。
