An attempt to promote neo-vascularization by employing a newly synthesized inhibitor of protein tyrosine phosphatase

Shinji Soeda, Takuji Shimada, Satoru Koyanagi, Tsutomu Yokomatsu, Tetsuo Murano, Shiroshi Shibuya, Hiroshi Shimeno

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Vascular endothelial growth factor (VEGF) and its receptors play a key role in angiogenesis. VEGF receptor-2 (VEGFR-2) has a tyrosine kinase domain, and, once activated, induces the phosphorylation of cytoplasmic signaling proteins. The phosphorylated VEGFR-2 may be a substrate for intracellular protein tyrosine phosphatases (PTPs) which prevent VEGF signaling. We synthesized a series of α,α-difluoro(phenyl)methylphosphonic acids (DFPMPAs) which inhibit the action of PTP. In this study, we test their effects on VEGF-induced angiogenesis. DFPMPA-3, the most effective inhibitor of human PTP-1B, promoted tube formation by human umbilical vein endothelial cells (HUVEC) on Matrigel more effectively than any other DFPMPAs. The inhibitor promoted the VEGF-induced proliferation and migration of HUVEC by inhibiting the dephosphorylation of VEGFR-2. Its effectiveness was proven through neo-vascularization in mice. The present findings suggest that targeting PTP to promote therapeutic neo-vascularization may be a potential strategy.

Original languageEnglish
Pages (from-to)54-58
Number of pages5
JournalFEBS Letters
Volume524
Issue number1-3
DOIs
Publication statusPublished - Jul 31 2002
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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