KGF-1 accelerates wound contraction through the TGF-β1/Smad signaling pathway in a double-paracrine manner.

KGF-1 plays an important role in the wound healing process. Loss of the KGF-1 gene in diabetic mice attenuated the process of wound contraction, suggesting that KGF-1 contributes to wound contraction. However, the mechanism remains unclear. To investigate the role of KGF-1 in diabetic wound contraction, we established a keratinocyte-fibroblast co-culture system. Concentrations of transforming growth factor β1 (TGF-β1) in conditioned supernatant treated with KGF-1 (KGF-1 group), tk;4KGF-1-neutralizing antibody (anti-KGF-1 group), TGF-β1 (TGF-β1tk;1 group), KGF-1 and TGF-β1-neutralizing antibody (KGF-1 + anti-TGF-β1 group) were tested by ELISA. Conditioned medium was added to fibroblast-populated collagen lattice (FPCL) to investigate the effect of KGF-1 on fibroblastqj contraction. TGF-β1, Col-I, p-Smad2, p-Smad3, and α-smooth muscle actin (α-SMA) were examined by Western blotting. A diabetic rat wound model was utilized to evaluate wound morphology, histology, immunohistochemistry, and protein expression in wound tissue after treatment with KGF-1. ELISA assays revealed that the concentration of TGF-β1 in the conditioned supernatant in the KGF-1 group was significantly higher. The contractile capacity of FPCL stimulated by conditioned medium derived from the KGF-1 group was significantly elevated; however, the contractile activity of FPCL induced by KGF-1 was attenuated by TGF-β1-neutralizing antibody. The Western blot results suggest that KGF-1 is able to stimulate TGF-β1 activation with increased Col-I, p-Smad2, p-Smad3, and α-SMA expression. Diabetic wounds treated with KGF-1 had a higher degree of contraction with significantly higher expression of TGF-β1, Col-I, p-Smad2, p-Smad3, and α-SMA. Our findings demonstrate that KGF-1 promotes fibroblast contraction and accelerates wound contraction via the TGF-β1/Smad signaling pathway in a double-paracrine manner.

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