Down-Regulation of miR-301a-3p Reduces Burn-Induced Vascular Endothelial Apoptosis by potentiating hMSC-Secreted IGF-1 and PI3K/Akt/FOXO3a Pathway

iScience

Huinan Yin¹  Huifeng Song²  Xiaotong Yue³  Xiuxiu Shi⁴  Xiaoteng Wang⁴  Xingxia Hao⁴  Hongjie Duan⁴  Yushou Wu⁴  Hongyu Wang⁴  Wei Liu⁴  Jiake Chai⁵  Yunfei Chi⁵  Shaofang Han⁵  Shaozeng Li⁵  Hailiang Bai⁵  Longlong Yang⁵  Qiong Wang⁵  Yang Chang⁶  Lingying Liu⁷ 

[1] Burns Institute of PLA, Department of Burn &College of Basic Medicine, the Inner Mongolia Medical University, Hohhot, 010110, Inner Mongolia, China;Corresponding author;Plastic Surgery, the Fourth Medical Center Affiliated to PLA General Hospital, Beijing 100037, China;;Burns Institute of PLA, Department of Burn &College of Basic Medicine, the Inner Mongolia Medical University, Hohhot, 010110, Inner Mongolia, China;Nutrition Department, the Fourth Medical Center Affiliated to PLA General Hospital, Beijing 100037, China;

关键词: Clinical Genetics;    Cellular Therapy;    Stem Cells Research;   

DOI  :  

来源: DOAJ

【 摘 要 】

Summary: Vascular endothelium dysfunction plays a pivotal role in the initiation and progression of multiple organ dysfunction. The mesenchymal stem cell (MSC) maintains vascular endothelial barrier survival via secreting bioactive factors. However, the mechanism of human umbilical cord MSC (hMSC) in protecting endothelial survival remains unclear. Here, we found IGF-1 secreted by hMSC suppressed severe burn-induced apoptosis of human umbilical vein endothelial cells (HUVECs) and alleviated the dysfunction of vascular endothelial barrier and multiple organs in severely burned rats. Severe burn repressed miR-301a-3p expression, which directly regulated IGF-1 synthesis and secretion in hMSC. Down-regulation of miR-301a-3p decreased HUVECs apoptosis, stabilized endothelial barrier permeability, and subsequently protected against multiple organ dysfunction in vivo. Additionally, miR-301a-3p negatively regulated PI3K/Akt/FOXO3 signaling through IGF-1. Taken together, our study highlights the protective function of IGF-1 against the dysfunction of multiple organs negatively regulated by miR-301a-3p, which may provide the theoretical foundation for further clinical application of hMSC.

【 授权许可】

Unknown