Wnt/β-catenin信号通路在TGF-β1诱导的真皮成纤维细胞向肌成纤维细胞表型转化中的作用及机制

项目名称： Wnt/β-catenin信号通路在TGF-β1诱导的真皮成纤维细胞向肌成纤维细胞表型转化中的作用及机制

项目编号： No.81201470

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学四处

项目作者： 刘佳琦

作者单位： 中国人民解放军第四军医大学

项目金额： 23万元

中文摘要： 肌成纤维细胞主要由成纤维细胞表型转化而来，是导致增生性瘢痕形成的关键细胞，但调控成纤维细胞向肌成纤维细胞转化的具体机制不清。课题组近期研究发现，Wnt/β-catenin通路可抑制TGF-β1诱导的成纤维细胞表型转化。据此提出，Wnt/β-catenin抑制真皮成纤维细胞表型转化，进而抑制增生性瘢痕的形成。本课题拟首先对Wnt/β-catenin通路上下游分子在不同时期瘢痕及其来源成纤维细胞中的表达进行检测，外源干预Wnt/β-catenin通路，观察其对成纤维细胞表型转化等生物学功能的影响和对TGF-β通路下游关键分子的作用，探讨Wnt/β-catenin与TGF-β信号通路交互调控作用的潜在机制，最后在增生性瘢痕成纤维细胞和兔耳瘢痕模型中进行验证。本研究旨在发现Wnt通路调控真皮成纤维细胞表型转化的机制，为阐明瘢痕形成机理提供新思路，为临床治疗增生性瘢痕提供理论基础。

中文关键词： 增生性瘢痕；成纤维细胞；转分化；Wnt；转化生长因子-b1

英文摘要： Myofibroblasts, which derived from fibroblasts, are key cells contributing to the pathogenesis of hypertrophic scar. However, the regulation mechanism of the fibroblasts-to-myofibroblasts transition is still unclear. Recently, our group has observed that Wnt/β-catenin inhibited the TGF-β1 induced myofibroblasts transition. Based on this observation, we hypothesize that Wnt/β-catenin inhibits the fibroblasts-to-myofibroblasts transition and thus inhibits the formation of hypertrophic scar. In the current research, the expression level of Wnt/β-catenin signal pathway components in hypertrophic scars at different stage and fibroblasts will be measured. Then, the effects of Wnt/β-catenin on myofibroblasts transition and the expression of TGF-β1/Smad signal components will be investigated by using recombinant Wnts cytokines, over-expression and RNAi of β-catenin. Lastly, the hypertrophic scar derived fibroblasts and rabbit ear hypertrophic scar model will be used to observe the effects of the Wnt/β-catenin on the formation and development of hypertrophic scar. This research aims to discover the regulation machanism of Wnt/β-catenin on the dermal fibroblasts-to-myofibroblasts transition, which will provide new clues for elucidating the machanism of hypertrophic scar formation and provide theoretical evidence for the e

英文关键词： Hypertrophic scar；fibroblasts；transdifferentiation；Wnt；TGF-b1