title: Basic fibroblast growth factor in an artificial dermis promotes apoptosis and inhibits expression of alpha-smooth muscle actin, leading to reduction of wound contraction.
abstract: 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 microg) and/or fibroblasts (1 x 10(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.
authors.affiliation: Department of Pathology, School of Medicine, Toho University, Ohta-City, Tokyo, Japan.
authors.forename: Yoshikiyo
authors.initials: Y
authors.lastname: Akasaka
authors.forename: Ichiro
authors.initials: I
authors.lastname: Ono
authors.forename: Akihiro
authors.initials: A
authors.lastname: Tominaga
authors.forename: Yukio
authors.initials: Y
authors.lastname: Ishikawa
authors.forename: Kinji
authors.initials: K
authors.lastname: Ito
authors.forename: Takeya
authors.initials: T
authors.lastname: Suzuki
authors.forename: Risa
authors.initials: R
authors.lastname: Imaizumi
authors.forename: Shigeki
authors.initials: S
authors.lastname: Ishiguro
authors.forename: Kowichi
authors.initials: K
authors.lastname: Jimbow
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Ishii
mesh_terms: D000199:Actins / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002921:Cicatrix / Q000517:prevention & control*; D003094:Collagen; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage / Q000494:pharmacology*; D007124:Immunoenzyme Techniques; D020287:In Situ Nick-End Labeling; D051381:Rats; D017208:Rats, Wistar; D017768:Skin, Artificial; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D000199:Actins; D003094:Collagen; D016222:Fibroblast Growth Factor 2; C498862:Acta2 protein, rat