Research Project
Grant-in-Aid for Scientific Research (C)
Vascular endothelial growth factor (VEGF) promotes the growth of vascular endothelial cells and the development of new blood vessels through interaction with VEGF receptor-2 (KDR/flk-1). The binding of VEGF to KDR/flk-1 induces conformational changes in the receptor, followed by dimerization and autophosphorylation of the tyrosine residues. The phosphorylated KDR/flk-1 can be a substrate for intracellular protein tyrosine phosphatases. SHP-1 , a cytoplasmic protein tyrosine phosphatase that contain two Src homology 2 domains in its N-terminal half, interacts with activated cytokine, growth factor, and antigen receptors and plays a negative regulatory role in signal transduction pathways by dephosphorylation of the receptors or receptor substrates to which it binds. Thus, therapeutic angiogenesis designed to inhibit expression of SHP-1 would be beneficial in hindlimb ischemia. Here we report that siRNA targeting SHP-1 activates KDR/flk-1 and accelerates angiogenesis in a rat model of hindlimb ischemia. Upon injection to the ischemic adductor muscle, vector-based siRNA reduced SHP-1, increased phosphorylation of KDR/flk-1, and markedly increased capillary density. Our data demonstrate in vivo the potential use of siRNA targeting SHP-1 as therapy for peripheral ischemic diseases.
All 2007 2006
All Journal Article (19 results) (of which Peer Reviewed: 7 results) Presentation (9 results)
Atherosclerosis 191
Pages: 33-39
Mol Cell Biochem 304
Pages: 353-360
J Neuropsychiatry Clin Neurosci 19
Pages: 342-343
Mol Cell Biochem. 304
Atherosclerosis. 19(1)
J. Neuropsychiat. Clin. Neurosci. (印刷中)(in press)
Cell Biochem Biophys 44
Pages: 65-71
Int J Cardiol 111
Pages: 405-412
Can J Physiol Pharmacol 84
Pages: 443-449
Cell Biochem Biophys 44(1)
Can J Physiol Pharmacol. 84(3-4)
Mol Cell Biochem. 294 (1-2)
Pages: 205-215
Cell Biochem Biophys. 44(1)
Int J Cardiol. 111(3)
