RUNX2 promotes epithelial differentiation of ADSCs and burn wound healing via targeting E-cadherin.
RUNX2 promotes epithelial differentiation of ADSCs and burn wound healing via targeting E-cadherin.
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RUNX2通过靶向E-钙粘蛋白促进ADSC上皮分化和烧伤创面愈合
DOI：
10.18632/oncotarget.23522
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发表时间：
2018-01-05
期刊：
影响因子：
--
通讯作者：
Jin P
中科院分区：
文献类型：
--
作者：
Li Q;Zhao H;Xia S;Wei H;Chen F;Jin P
脂肪源性干细胞（ADSCs）的上皮分化是由多种分子功能和生物过程（包括转录调节）的复杂相互作用介导的。runt相关转录因子2 （RUNX2）促进ADSCs成骨细胞和脂肪细胞分化。然而，RUNX2在ADSCs上皮分化中的作用尚不清楚。我们首先证明了ADSCs具有分化为上皮谱系的潜力。然后，我们利用RUNX2对ADSCs上皮分化的影响。我们的数据显示，RUNX2促进了ADSCs的上皮分化。RUNX2过表达或敲低分别导致E-cadherin表达升高或降低。在ADSCs中减少E-cadherin会减弱runx2激活的ADSCs和上皮标记物细胞角蛋白18 （CK18）和闭塞带蛋白1 （ZO-1）的上皮转化。我们还在体内评估了RUNX2对烧伤创面愈合的影响。RUNX2可促进创面再上皮化。创面闭合指数、半瓣再生及血运重建均有改善。此外，通过染色质免疫沉淀（ChIP）和荧光素酶启动子报告基因检测，在ADSCs中表征了RUNX2直接结合E-cadherin启动子区域。综上所述，本研究证明了RUNX2在ADSCs上皮分化中的作用，并表明RUNX2至少在一定程度上通过与启动子的直接结合促进E-cadherin的表达。
Epithelial differentiation of adipose-derived stem cells (ADSCs) is mediated by sophisticated interactions of various molecular functions and biological processes, including transcriptional regulation. Runt-related transcription factor 2 (RUNX2) increases osteoblast and adipocyte differentiation of ADSCs. However, the role of RUNX2 in epithelial differentiation of ADSCs is unknown. We first showed that ADSCs possess the potential to differentiate into epithelial lineage. Then, we employed the effect of RUNX2 on epithelial differentiation of ADSCs. Our data showed that RUNX2 promoted epithelial differentiation of ADSCs. Overexpression or knockdown of RUNX2 resulted in increase or decrease of E-cadherin expression, respectively. Abatement of E-cadherin in ADSCs attenuated RUNX2-activated epithelial conversion of ADSCs and epithelial markers cytokeratin 18 (CK18) and zonula occludens protein-1 (ZO-1). We also evaluated the effect of RUNX2 on burn wound healing in vivo. The wound re-epithelialization were accelerated by RUNX2. The wound closure indexs, demis regeneration and revascularization were all improved. Furthermore, RUNX2 binding directly to the E-cadherin promoter region was characterized in ADSCs by chromatin immunoprecipitation (ChIP) and luciferase promoter reporter assays. Taken together, the study demonstrates the role of RUNX2 in epithelial differentiation of ADSCs and suggests that RUNX2 promotes E-cadherin expression, at least in part, through its direct binding to the promoter.
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