The Vascular Endothelial Growth Factors-Expressing Character of Mesenchymal Stem Cells Plays a Positive Role in Treatment of Acute Lung Injury In Vivo.
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.
Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, No. 87 Dingjiaqiao Road, Nanjing, Jiangsu 210009, China.
Yi
Y
Yang
School of Medicine, Southeast University, No. 87 Dingjiaqiao Road, Nanjing, Jiangsu 210009, China.
Shuling
S
Hu
School of Medicine, Southeast University, No. 87 Dingjiaqiao Road, Nanjing, Jiangsu 210009, China.
Xiuping
X
Xu
School of Medicine, Southeast University, No. 87 Dingjiaqiao Road, Nanjing, Jiangsu 210009, China.
Jinze
J
Li
Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, No. 87 Dingjiaqiao Road, Nanjing, Jiangsu 210009, China.
Airan
A
Liu
School of Medicine, Southeast University, No. 87 Dingjiaqiao Road, Nanjing, Jiangsu 210009, China.
Jibin
J
Han
Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, No. 87 Dingjiaqiao Road, Nanjing, Jiangsu 210009, China.
Songqiao
S
Liu
Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, No. 87 Dingjiaqiao Road, Nanjing, Jiangsu 210009, China.
Ling
L
Liu
Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, No. 87 Dingjiaqiao Road, Nanjing, Jiangsu 210009, China.
Haibo
H
Qiu
D055371:Acute Lung Injury / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000628:therapy; D000818:Animals; D002478:Cells, Cultured; D004487:Edema / Q000378:metabolism / Q000473:pathology; D005455:Fluorescent Antibody Technique; D020287:In Situ Nick-End Labeling; D016753:Interleukin-10 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008297:Male; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D042442:Vascular Endothelial Growth Factors / Q000235:genetics / Q000378:metabolism*
D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D042442:Vascular Endothelial Growth Factors; D016753:Interleukin-10