Plasminogen activator inhibitor-I–related regulation of procollagen I (α1 and α2) by antitransforming growth factor-β1 treatment during radiation-impaired wound healing

Purpose: Plasminogen activator inhibitor (PAI)-1 mediates transforming growth factor-β 1 (TGF-β 1 )–related signaling by stimulating collagen Type I synthesis in radiation-impaired wound healing. The regulation of α(I)-procollagen is contradictory in fibroblasts of different fibrotic lesions. It is not known whether anti–TGF-β 1 treatment specifically inhibits α(I)-procollagen synthesis. We used an experimental wound healing study to address anti–TGF-β 1 –associated influence on α(I)-procollagen synthesis. Methods and Materials: A free flap was transplanted into the preirradiated (40 Gy) or nonirradiated neck region of Wistar rats: Group 1 ( n = 8) surgery alone; Group 2 ( n = 14) irradiation and surgery; Group 3 ( n = 8) irradiation and surgery and anti–TGF-β 1 treatment. On the 14th postoperative day, skin samples were processed for fibroblast culture, in situ hybridization for TGF-β 1 , immunohistochemistry, and immunoblotting for PAI-1, α 1 /α 2 (I)-procollagen. Results: Anti–TGF-β 1 significantly reduced TGF-β 1 mRNA ( p p 1 treatment in vivo significantly reduced α 1 (I)-procollagen protein ( p p p 2 (I)-procollagen expression. Conclusion: These results emphasize anti–TGF-β 1 treatment to reduce radiation-induced fibrosis by decreasing α 1 (I)-procollagen synthesis in vivo . α 1 (I)-procollagen and α 2 (I)-procollagen might be differentially regulated by anti–TGF-β 1 treatment. Increased TGF-β signaling in irradiated skin fibroblasts seemed to be reversible, as shown by a reduction in PAI-1 expression after anti–TGF-β 1 treatment.