Yang Yi, Hu Shuling, Xu Xiuping, Li Jinze, Liu Airan, Han Jibin, Liu Songqiao, Liu Ling, Qiu Haibo
Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, No. 87 Dingjiaqiao Road, Nanjing, Jiangsu 210009, China.
School of Medicine, Southeast University, No. 87 Dingjiaqiao Road, Nanjing, Jiangsu 210009, China.
Mediators Inflamm. 2016;2016:2347938. doi: 10.1155/2016/2347938. Epub 2016 May 24.
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.
最近,间充质干细胞(MSC)已被证明对急性呼吸窘迫综合征(ARDS)有益。血管内皮生长因子(VEGF)是MSC释放的一种重要血管生成因子。然而,MSC表达VEGF的特性在MSC治疗ARDS中的精确作用仍不清楚。在此,我们首先通过慢病毒转导敲低MSC中的VEGF基因(MSC-ShVEGF)。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)大鼠体内。数据显示,MSC移植显著提高了肺组织中的VEGF水平,降低了肺通透性,保护肺内皮细胞免于凋亡,促进VE-钙黏蛋白恢复,控制炎症,并减轻了肺损伤。然而,敲低MSC中的VEGF基因导致损伤肺组织中VEGF表达相对不足,并显著降低了MSC对ALI的治疗效果,这表明MSC表达VEGF的行为在维持肺组织中VEGF水平以及MSC治疗ALI中起重要作用。因此,我们得出结论,MSC部分通过维持肺组织中“足够”的VEGF水平来恢复ALI大鼠的肺通透性并减轻肺损伤,且MSC表达VEGF的特性在MSC治疗ARDS的疗效中发挥积极作用。