Oncotarget

Research Papers:

Suppression of microRNA-205-5p in human mesenchymal stem cells improves their therapeutic potential in treating diabetic foot disease

Lingyan Zhu, Gongxian Wang, Shane Fischbach and Xiangwei Xiao _

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Oncotarget. 2017; 8:52294-52303. https://doi.org/10.18632/oncotarget.17012

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Abstract

Lingyan Zhu1, Gongxian Wang2,*, Shane Fischbach3 and Xiangwei Xiao3,*

1Department of Endocrinology, The First Affiliated Hospital of Nanchang University, Nanchang 330006, China

2Department of Urology, The First Affiliated Hospital of Nanchang University, Nanchang 330006, China

3Division of Pediatric Surgery, Department of Surgery, Children’s Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, PA15224, USA

*These authors contributed equally to this work

Correspondence to:

Xiangwei Xiao, email: xiangwei.xiao@chp.edu

Gongxian Wang, email: wanggx-mr@126.com

Keywords: diabetic foot disease (DF), microRNA, mesenchymal stem cells (MSCs), vascular endothelial growth factor (VEGF)

Received: March 21, 2017     Accepted: March 30, 2017     Published: April 10, 2017

ABSTRACT

Diabetes is a prevalent disease endangering human health, while diabetic foot disease (DF) is one of the most severe complications of diabetes. Mesenchymal stem cells (MSCs) have been used in DF treatment, taking advantage of the differentiation potential of MSCs into endothelial cells and their production and secretion of trophic factors like vascular endothelial growth factor (VEGF). Molecular modification of MSCs to improve their therapeutic effects has been recently applied in treating other diseases, but not yet in DF. Here, we found that micoRNA-205-5p (miR-205-5p) is expressed in human MSCs, and miR-205-5p inhibits protein translation of VEGF through its interaction with 3’-UTR of the VEGF mRNA. Expression of antisense of miR-205-5p (as-miR-205-5p) significantly increased both cellular and secreted VEGF by MSCs, which significantly improved the therapeutic effects of MSCs on DF-associated wound healing in diabetic NOD/SCID mice. Together, our data suggest that miR-205-5p suppression in MSCs may improve their therapeutic effects on DF, seemingly through augmentation of VEGF-mediated vascularization.


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