RUNX2靶向E-cadherin对ADSCs表皮分化及烧伤创面修复影响及其机制

寻找充足的表皮来源是促进烧伤创面愈合关键。ADSCs可向表皮分化，但分化效率偏低。申请者前期发现。ADSCs过表达RUNX2，细胞表皮分化能力及E-Cadherin水平显著提高，CRISPR-Cas9基因敲除RUNX2， ADSCs表皮分化能力和E-Cadherin表达下降；ADSCs过表达E-Cadherin，细胞表皮分化能力显著提高。同时，软件分析发现，RUNX2可结合E-cadherin核心启动子。因而提出：RUNX2通过E-Cadherin调控ADSCs表皮分化。 .因此，我们拟应用过表达、基因敲除、点突变和CRISPR-Cas9系统等技术，从细胞、分子和整体水平阐明RUNX2在ADSCs表皮分化中的作用及可能机制，并探讨CRISPR-Cas9系统靶向激活E-Cadherin启动子的可行性及其可能的治疗作用，为提高ADSCs表皮分化效率、促进烧伤创面表皮修复奠定基础。

Plenty of sources of epidermis are critical to promote burn wound healing. ADSCs can differentiate into epidermis, but the efficiency of epidermal differentiation is pretty low. Our previous data indicated that over-expression of RUNX2 in ADSCs can promote epidermal differentiation of ADSCs and enhance the expression of E-cadherin. RUNX2 Knockout by CRISPR-Cas9 system can significantly inhibit epidermal differentiation of ADSCs and E-cadherin expression. By means of software analysis, we found that the promotor of E-cadherin may have potential binding sites for RUNX2. Based on the above data, we made the assumption that RUNX2 improves epidermal differentiation of ADSCs through the enhanced expression of E-Cadherin. So we chose to focus on this pathway for our investigatin, and we intend to clarify the possible mechanisms by which RUNX2 enhances the epidermal differentiation of ADSCs. This study may offer a novel target for effective enhancement in ADSCs differentiation into epidermal cells and improvement of burn wound healing.