摘要：SummaryVascular 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 dysfunctionin 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.Graphical AbstractDisplay OmittedHighlights•IGF-1 secreted by hMSC suppressed severe burn-induced apoptosis of HUVECs•miR-301a-3p directly regulated IGF-1 synthesis and secretion in hMSC•Down-regulation of miR-301a-3p protected against multiple organ dysfunction•miR-301a-3p regulated PI3K/Akt/FOXO3 signaling through hMSC-secreted IGF-1Clinical Genetics; Cellular Therapy; Stem Cells Research
