The Vascular Endothelial Growth Factors-Expressing Character of Mesenchymal Stem Cells Plays a Positive Role in Treatment of Acute Lung Injury In Vivo.

The Vascular Endothelial Growth Factors-Expressing Character of Mesenchymal Stem Cells Plays a Positive Role in Treatment of Acute Lung Injury In Vivo.
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间充质干细胞的血管内皮生长因子表达特性在体内治疗急性肺损伤中发挥积极作用

DOI:
10.1155/2016/2347938
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发表时间:
2016
影响因子:
4.6
通讯作者:
Qiu H
Qiu H
中科院分区:
医学3区
文献类型:
--
作者:
Yang Y;Hu S;Xu X;Li J;Liu A;Han J;Liu S;Liu L;Qiu H

文献摘要

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最近,间充质干细胞(MSC)已被证明对治疗急性呼吸窘迫综合征(ARDS)有益。血管内皮生长因子(VEGF)是MSC释放的重要血管生成因子。然而,MSC 的 VEGF 表达特征在 MSC 治疗 ARDS 中的确切作用仍不清楚。在这里,我们首先通过慢病毒转导敲低MSC(MSC-ShVEGF)中的VEGF基因。然后,我们通过尾静脉将 MSC-ShVEGF 注射到脂多糖诱导的急性肺损伤 (ALI) 大鼠中。数据显示,MSC移植显着增加肺内VEGF水平,降低肺通透性,保护肺内皮细胞免于凋亡,促进VE-钙粘蛋白恢复,控制炎症,减轻肺损伤。然而,MSC中VEGF基因敲除导致受损肺中VEGF表达相对不足,并显着降低了MSC对ALI的治疗效果,这表明MSC的VEGF表达行为在维持肺中VEGF以及MSC治疗ALI中发挥着重要作用。因此,我们得出结论,MSC 可以部分通过维持肺中“足够”的 VEGF 水平来恢复 ALI 大鼠的肺通透性并减轻肺损伤,并且 MSC 的 VEGF 表达特性在 MSC 对 ARDS 的治疗作用中发挥着积极作用。
Recently, mesenchymal stem cells (MSC) have been proved to be beneficial in acute respiratory distress syndrome (ARDS). Vascular endothelial growth factor (VEGF) is an important angiogenesis factor that MSC release. However, the precise role of VEGF-expressing character of MSC in the MSC treatment for ARDS remains obscure. Here, we firstly knocked down the gene VEGF in MSC (MSC-ShVEGF) with lentiviral transduction. Then we injected the MSC-ShVEGF to rats with lipopolysaccharide-induced acute lung injury (ALI) via the tail vein. Data showed that MSC transplantation significantly increased VEGF levels in the lung, reduced lung permeability, protected lung endothelium from apoptosis, facilitated VE-cadherin recovery, controlled inflammation, and attenuated lung injury. However, VEGF gene knockdown in MSC led to relatively insufficient VEGF expression in the injured lung and significantly diminished the therapeutic effects of MSC on ALI, suggesting an important role of VEGF-expressing behavior of MSC in the maintenance of VEGF in the lung and the MSC treatment for ALI. Hence, we conclude that MSC restores the lung permeability and attenuates lung injury in rats with ALI in part by maintaining a “sufficient” VEGF level in the lung and the VEGF-expressing character of MSC plays a positive role in the therapeutic effects of MSC on ARDS.