Basic fibroblast growth factor in an artificial dermis promotes apoptosis and inhibits expression of α-smooth muscle actin, leading to reduction of wound contraction
Basic fibroblast growth factor in an artificial dermis promotes apoptosis and inhibits expression of α-smooth muscle actin, leading to reduction of wound contraction
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DOI：
10.1111/j.1524-475x.2007.00240.x
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发表时间：
2007-05-01
影响因子：
2.9
通讯作者：
Ishii, Toshiharu
中科院分区：
文献类型：
--
作者：
Akasaka, Yoshikiyo;Ono, Ichiro;Ishii, Toshiharu
为了阐明碱性成纤维细胞生长因子（bFGF）引起的伤口收缩下降的潜在机制以及自体成纤维细胞在调节伤口愈合中的作用，我们检测了α-平滑肌肌动蛋白的表达，使用含和不含bFGF（1 μ g）和/或成纤维细胞（1x 10（6）个细胞/cm（2））的胶原海绵的伤口愈合模型中的α-SMA和细胞凋亡应用于大鼠实验产生的全层皮肤伤口（每组n=10）。术后7天，与仅填充胶原海绵的对照伤口（对照组）相比，填充成纤维细胞接种胶原海绵的伤口（成纤维细胞接种组）显示胶原海绵面积更大，成纤维细胞面积更小。因此，在真皮替代物中接种成纤维细胞可以延缓胶原海绵的降解，抑制成纤维细胞浸润到替代物中。到第14天，与其他伤口相比，用bFGF处理的胶原海绵填充而没有成纤维细胞接种的伤口（bFGF组）显示出α-SMA表达降低和细胞凋亡显著增加。双重染色显示bFGF组中α-SMA阳性成纤维细胞的凋亡显著增加，表明bFGF治疗是肌成纤维细胞凋亡的有效刺激物。此外，形态学分析表明，在第42天，bFGF组的伤口收缩水平和成熟胶原束形成的程度显著降低。bFGF组在第28天也显示巨噬细胞中bFGF表达增加。这些结果表明，向人工真皮给予bFGF可促进α-SMA阳性成纤维细胞的凋亡并抑制治疗伤口中的α-SMA表达，从而减少伤口收缩。
To clarify the mechanisms underlying declines in wound contraction caused by basic fibroblast growth factor (bFGF) and the role of autologous fibroblasts in modulating wound healing, we have examined the expression of alpha-smooth muscle actin (alpha-SMA) and apoptosis in a model of wound healing using collagen sponges with and without bFGF (1 mu g) and/or fibroblasts (1x10(6)cells/cm(2)) applied to experimentally produced full-thickness skin wounds in rats (n=10 for each group). At 7 days postoperatively, wounds filled with a fibroblast-seeded collagen sponge (fibroblast-seeded group) displayed a greater area of collagen sponge and a smaller area of fibroblasts compared with control wounds filled with collagen sponge alone (control group). Therefore, seeding of fibroblasts in the dermal substitute might retard degradation of the collagen sponge, inhibiting fibroblast infiltration into the substitute. By day 14, wounds filled with bFGF-treated collagen sponge without fibroblast seeding (bFGF group) displayed decreased alpha-SMA expression and significantly increased apoptosis compared with other wounds. Double staining revealed that apoptosis in alpha-SMA-positive fibroblastic cells was significantly increased in the bFGF group, suggesting that bFGF treatment is a potent stimulator of myofibroblast apoptosis. Furthermore, morphometric analysis demonstrated the significant decrease in the level of wound contraction and the degree of mature collagen bundle formation in the bFGF group by day 42. The bFGF group also showed increased bFGF expression in macrophages by day 28. These results suggest that bFGF administration to an artificial dermis promotes apoptosis of alpha-SMA-positive fibroblastic cells and inhibits alpha-SMA expression in the treated wound, thus reducing wound contraction.