Transforming growth factor-beta1 enhanced vascular endothelial growth factor synthesis in mesenchymal stem cells.
Angiogenesis is essential for transplantation of mesenchymal stem cells (MSCs). Vascular endothelial growth factor (VEGF) is one of the most potent angiogenic factors identified to date. Elevated VEGF levels in MSCs correlate with the potential of MSCs transplantation. As an indirect angiogenic agent, transforming growth factor-beta1 (TGF-beta1) plays a pivotal role in the regulation of vasculogenesis and angiogenesis. However, the effect of TGF-beta1 on VEGF synthesis in MSCs is still unknown. Besides, the intracellular signaling mechanism by which TGF-beta1 stimulates this process remains poorly understood. In this article, we demonstrated that exposure of MSCs to TGF-beta1 stimulated the synthesis of VEGF. Meanwhile, TGF-beta1 stimulated the phosphorylation of Akt and extracellular signal-regulated kinase 1/2 (ERK1/2). Moreover, Ly 294002, a specific inhibitor of phosphatidylinositol-3-kinase (PI3K)/Akt significantly attenuated the VEGF synthesis stimulated by TGF-beta1. Additionally, U0126, a specific inhibitor of ERK1/2, also significantly attenuated the TGF-beta1-stimulated VEGF synthesis. These results indicated that TGF-beta1 enhanced VEGF synthesis in MSCs, and the Akt and ERK1/2 activation were involved in this process.
Wang
Xiao-Jun
XJ
Department of Pharmacology, Nanjing Medical University, 140 Hanzhong Road, Nanjing, Jiangsu [corrected] 210029, China.
Dong
Zhan
Z
Zhong
Xiao-Hua
XH
Shi
Rui-Zhen
RZ
Huang
Song-Hua
SH
Lou
Yue
Y
Li
Qing-Ping
QP
D000818:Animals; D002070:Butadienes / Q000494:pharmacology; D059630:Mesenchymal Stem Cells / Q000187:drug effects* / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D009570:Nitriles / Q000494:pharmacology; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*
D002070:Butadienes; D009570:Nitriles; D047428:Protein Kinase Inhibitors; D053773:Transforming Growth Factor beta1; C113580:U 0126; D042461:Vascular Endothelial Growth Factor A; D051057:Proto-Oncogene Proteins c-akt; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3