Down-Regulation of miR-301a-3p Reduces Burn-Induced Vascular Endothelial Apoptosis by potentiating hMSC-Secreted IGF-1 and PI3K/Akt/FOXO3a Pathway
Down-Regulation of miR-301a-3p Reduces Burn-Induced Vascular Endothelial Apoptosis by potentiating hMSC-Secreted IGF-1 and PI3K/Akt/FOXO3a Pathway
复制标题
miR-301a-3p 的下调通过增强 hMSC 分泌的 IGF-1 和 PI3K/Akt/FOXO3a 途径减少烧伤诱导的血管内皮细胞凋亡
DOI：
10.1016/j.isci.2020.101383
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发表时间：
2020-08-21
期刊：
影响因子：
5.8
通讯作者：
Li, Shaozeng
中科院分区：
文献类型：
--
作者：
Liu, Lingying;Yin, Huinan;Li, Shaozeng
血管内皮功能障碍在多器官功能障碍的发生和发展中起着关键作用。间充质干细胞（mesenchymal stem cell，MSC）通过分泌生物活性因子维持血管内皮屏障的存活。然而，人脐带间充质干细胞（hMSC）保护内皮细胞存活的机制尚不清楚。本研究发现，hMSC分泌的IGF-1可抑制严重烧伤诱导的人脐静脉内皮细胞（HUVECs）凋亡，减轻严重烧伤大鼠血管内皮屏障和多器官功能障碍。严重烧伤抑制miR-301 a-3 p的表达，miR-301 a-3 p直接调节hMSC中IGF-1的合成和分泌。下调miR-301 a-3 p可减少HUVEC凋亡，稳定内皮屏障通透性，随后保护其免受体内多器官功能障碍。此外，miR-301 a-3 p通过IGF-1负调控PI 3 K/Akt/FOXO 3信号传导。综上所述，本研究揭示了IGF-1对miR-301 a-3 p负调控的多器官功能障碍的保护作用，为hMSC的进一步临床应用提供了理论基础。
Vascular endothelium dysfunction plays a pivotal role in the initiation and pro-gression 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 endo-thelial 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 protec-tive function of IGF-1 against the dysfunction of multiple organs negatively regu-lated by miR-301a-3p, which may provide the theoretical foundation for further clinical application of hMSC.