Abstract
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.
Highlights
Burn wounds, the thermal damage to the skin, can lead to severe complications and have been demonstrated to have a devastating effect on skin functionally and cosmetically, necessitating the search for a better and more efficient cure
The expression of Runt-related transcription factor 2 (RUNX2) and E-cadherin are up-regulated during epithelial differentiation of adipose-derived stem cells (ADSCs)
Our results suggested that ADSCs possess the potential to differentiate into epithelial lineage
Summary
The thermal damage to the skin, can lead to severe complications and have been demonstrated to have a devastating effect on skin functionally and cosmetically, necessitating the search for a better and more efficient cure. Due to the introduction of treatment modalities with the application of stem cells, the regenerative medicine has been revolutionized. In the field of wound healing, the use of stem cells has been reported for curing different types of wounds [1, 2]. Studies have shown the efficacy of stem cells in promoting faster and superior burn wounds healing [3]. The use of stem cells may open up a new arena of possibilities to improve wound healing in burn patients. Mesenchymal stem cells (MSCs) are multipotent cells capable of self-renewal and differentiation into tissue-specific cell types. Among the various sources of MSCs, ADSCs are abundant and obtained from subcutaneous adipose tissue via liposuction in the clinic [4, www.impactjournals.com/oncotarget
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