Basic fibroblast growth factor in an artificial dermis promotes apoptosis and inhibits expression of a-smooth muscle actin, leading to reduction of wound contraction

• Published in: Wound repair and regeneration Vol. 15; no. 3; pp. 378 - 389
• Main Authors: Akasaka, Yoshikiyo, Ono, Ichiro, Tominaga, Akihiro, Ishikawa, Yukio, Ito, Kinji, Suzuki, Takeya, Imaizumi, Risa, Ishiguro, Shigeki, Jimbow, Kowichi, Ishii, Toshiharu
• Format: Journal Article
• Language: English
• Published: 01.05.2007
• DOI: 10.1111/j.1524-475X.2007.00240.x
• ISSN: 1067-1927

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 a-smooth muscle actin (a-SMA) and apoptosis in a model of wound healing using collagen sponges with and without bFGF (1 kg) and-or fibroblasts (1 x 10 super(6) cells-cm super(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 a-SMA expression and significantly increased apoptosis compared with other wounds. Double staining revealed that apoptosis in a-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 a-SMA-positive fibroblastic cells and inhibits a-SMA expression in the treated wound, thus reducing wound contraction.