RUNX2 promotes epithelial differentiation of ADSCs and burn wound healing via targeting E-cadherin
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Qiang Li1,*, Han Zhao1,3,*, Sizhan Xia1, Hanxiao Wei1, Feifei Chen2 and Peisheng Jin1
1Department of Plastic Surgery, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China
2Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China
3Department of Plastic Surgery, Xuzhou Central Hospital, Xuzhou, Jiangsu, China
*These authors have contributed equally to this work
Peisheng Jin, email: firstname.lastname@example.org
Feifei Chen, email: email@example.com
Keywords: RUNX2; E-cadherin; epithelial differentiation; burn wound; ADSCs
Received: June 06, 2017 Accepted: September 21, 2017 Published: December 21, 2017
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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