Angiotensin II induces vascular endothelial growth factor synthesis in mesenchymal stem cells.
Mesenchymal stem cells (MSCs) transplantation has been proposed as a promising means for ischemic heart disease. Vascular endothelial growth factor (VEGF) has been demonstrated to play an important role in MSCs transplantation. Angiotensin II (AngII), the most important effector peptide of the renin-angiotensin system (RAS), is also an angiogenesis factor. However, the effects of AngII on VEGF expression in MSCs and the related signaling cascades were unknown. In this experiment, we first demonstrated that incubation of MSCs with AngII-induced a rapid increase in VEGF mRNA expression and protein synthesis. However, these effects were abolished by prior treatment with AngII type 1 (AT(1)) receptor antagonist losartan while not AngII type 2 (AT(2)) receptor antagonist PD123319. The addition of either the extracellular signal-regulated kinase 1/2 (ERK1/2) inhibitor U0126 or Akt inhibitor LY294002 also led to a marked inhibition of the AngII-induced VEGF mRNA and protein production. Taken together, these results suggested that AngII stimulated the synthesis of VEGF in MSCs through ERK1/2 and Akt pathway via AT(1) receptor.
Shi
Rui-Zhen
RZ
Department of Pharmacology, Nanjing Medical University, 140 Hanzhong Road, Nanjing 210029, China.
Wang
Ji-Chang
JC
Huang
Song-Hua
SH
Wang
Xiao-Jun
XJ
Li
Qing-Ping
QP
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D059630:Mesenchymal Stem Cells / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis* / Q000235:genetics
D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D042461:Vascular Endothelial Growth Factor A; D000804:Angiotensin II; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases