增生性瘢痕中基底膜基质对表皮分化成熟和S100A8/A9的影响及其导致成纤维细胞活化的研究

项目名称： 增生性瘢痕中基底膜基质对表皮分化成熟和S100A8/A9的影响及其导致成纤维细胞活化的研究

项目编号： No.81501674

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 钟爱梅

作者单位： 华中科技大学

项目金额： 18万元

中文摘要： 增生性瘢痕作为创面愈合后最常见的并发症之一，相关研究一直是外科修复领域的热点和难点。表皮在调节深部结缔组织和皮肤损伤修复中具有重要作用，但是在瘢痕形成过程中，其调节途径和方式仍不明确。前期研究显示，S100A8/A9的水平在增生活跃的瘢痕表皮中高表达；失水能促使表皮角质形成细胞的众多炎症因子，包括S100A8/A9的表达水平上调，而S100A8/A9将进一步促发成纤维细胞的活化，这种从角质形成细胞出发的真皮纤维化研究为探索增生性瘢痕的发生机制提供了新的思路。但在这个过程中，角质形成细胞的被调控机制还不甚明确。由于基底膜基质对角质形成细胞的分化成熟至关重要，于是我们推测基底膜基质可能在瘢痕角质形成细胞的被调控过程中扮演了重要角色。本研究拟通过建立瘢痕体外培养模型，探究基底膜基质对角质形成细胞分化成熟及真皮成纤维细胞活化的影响及作用途径，这将为阐明增生性瘢痕的形成及发展提供新的理论和实验依据。

中文关键词： 增生性瘢痕；基底膜基质；角质形成细胞；成纤维细胞；S100A8/S100A9

英文摘要： Hypertrophic scar is one of the most common complication of wound healing, which is a focus and difficulty in the field of surgical restoration due to the intricate mechanisms. Epidermis plays an essential role in modulating subjacent connective tissue and wound healing of skin. However, its role in scar formation is not well charted yet. Our previous study shows that S100A8/A9 are highly expressed in the epidermis of human hypertrophic scar tissues compared to normal skin. Reduced hydration up-regulates the expression of many genes including S100A8/A9 in the epidermis, then S100A8/A9 activate dermal fibroblasts. This investigation on dermal fibrosis focusing on keratinocyte supplied a novel idea to explore the mechanism of hypertrophic scar. Adjusting mechanism of keratinocyte in this process has not been elucidated. Due to the critical role of basement membrane matrix on the differentiation and mutation of keratinocyte, we speculate that the basement membrane matrix is implicated in modulating keratinocyte and fibroblast in scar. In this study, we attempt to investigate the effect and pathway of basement membrane matrix on the differentiation and mutation of keratinocytes and activation of dermal fibroblasts through in vitro scar culture model, which provides a novel theoretical and experimental basis to elucidate the formation of hyperplastic scar.

英文关键词： Hypertrophic Scar;Basement membrane matrix;Keratinocyte;Fibroblast;S100A8/S100A9