张力可引导皮肤再生，但在临床治疗中，存在皮肤再生衰竭的现象，其机制不明。项目组研究发现张力刺激下的皮肤干细胞早期增殖活跃，而后期活性显著下降，补充干细胞可有效改变这一趋势（Ann Surg, 2011; Stem Cells, 2013），表明张力诱导皮肤再生与干细胞状态密切相关。现有研究表明，皮肤干细胞状态是由皮肤干细胞niche这一特殊结构决定的。项目组进一步研究发现，张力可通过Cadherin（CDH1）和Yap对基因修饰，实现对皮肤干细胞的激活和抑制（Cell Mol Life Sci, 2015）。基于上述发现，本项目提出“张力对皮肤再生具有双向调控作用”的假说，即张力通过CDH1和Yap影响下游的Wnt通路，作用于皮肤干细胞niche，激活或抑制皮肤干细胞，来实现对皮肤再生的调控。拟通过在体示踪模型建立和应用细胞分选技术和组学方法等，阐明张力调控皮肤再生的关键信号通路和机制。

Mechanical stretch can induce effective but limited skin regeneration. The delpetion in skin regeneration after long-term stretch is a obstacle in promoting its clicical applications. In our previous study, we proved that stem cell transplantation treatment in time can significantly pormote skin regenerative capacity under mechanical stretch (Ann Surg, 2011; Stem Cells,2013). We propose a new hypothesis that skin undergoes long-time stretch is induced to regenerative exhaustion. Meanwhile, results of our preliminary study demonstrated that mechanical stretch could both provoke skin regeneration via CDH1 pathway and suppress skin regeneration via regulating Yap pathway (Cell Mol Life Sci, 2015). On the basis of the preliminary study, the purpose of this project is trying to understand the mechanism of mechanical stretch induced skin regeneration and regenerative exhaustion. We hope that this project could explore the key regulator and pathway in mechanical stretch induced skin regeneration and help to clinical strategy innovation.