过去的研究表明皮肤成纤维细胞能分泌角质细胞生长因子-1（KGF-1），从而促进角质细胞的增殖和分化。在申请者前期工作中，通过在KGF-1基因敲除的糖尿病小鼠背部建立全层创面，我们发现KGF-1的缺失造成创面的收缩能力下降，说明KGF-1能作用于影响创面收缩的成纤维细胞。由于成纤维细胞上不存在KGF-1受体，KGF-1无法直接作用于成纤维细胞。而角质细胞能分泌转化生长因子-β1（TGF-β1），我们推断KGF-1通过诱导角质细胞分泌TGF-β1作用于成纤维细胞。为了证实该双旁分泌信号途径参与影响创面收缩，我们将通过角质细胞-成纤维细胞共培养系统中KGF-1的"表达下调"或"表达上调"来研究KGF-1对成纤维细胞分化和收缩的影响；同时从活体的角度,通过基因转染以增强小鼠创面KGF-1的表达，来研究KGF-1对创面收缩的作用机制。本项目对于探索KGF-1对创面收缩和愈合的作用机制有着重要的意义。

Keratinocyte growth factor-1(KGF-1) synthesized by fibroblasts can stimulate migration and proliferation of keratinocytes. In our previous study, we established a wound model on KGF-1 knockout diabetic mice and found that the wound contraction rate was significantly reduced due to the lack of KGF-1 in diabetic mice. These results indicate that KGF-1 can affect fibroblasts-mediated wound contraction. Since KGF-1 receptors are not found on fibroblasts, KGF-1 cannot directly act on fibroblasts. However, keratinocytes can secret TGF-β1 post-trauma. We hypothesize that KGF-1stimulate keratinocytes to secret TGF-β1, thus promoting the differentiation of fibroblast to myofibroblast. In order to confirm the effects of KGF-1 on the contraction and differentiation of fibroblast via double paracrine signaling, we will explore the mechanism by elevating or reducing the expression of KGF-1 in keratinocyte-fibroblast co-culture systems. In addition, we will enhance wound KGF-1 expression by transfecting KGF cDNA to mice wounds to observe the effects of KGF-1 on wound contraction. This study will significantly improve our understanding of the role of KGF-1 and the precise mechanisms of how keraticnocytes interact with fibroblasts in wound contraction and healing.