Stimulation of cell-surface urokinase-type plasminogen activator and cell migration in vascular endothelial cells by a novel hexapeptide analogue of neurotensin

Shin Ushiro, Kazushige Mizoguchi, Shigeo Yoshida, Sei Ichiro Jimi, Tadami Fujiwara, Masaya Yoshida, Edward T. Wei, Patrick Kitabgi, Sakae Amagaya, Mayumi Ono, Michihiko Kuwano

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Abstract

To investigate if neurotensin (NT) could induce activation of urokinase-type plasminogen activator (uPA) in vascular endothelial cells, we utilized the acetyl-NT (8-13) analogue, TJN-950, in which the C-terminal leucine is reduced to leucinol, TJN-950 inhibited the binding of 125I-NT to membranes of newborn rat brains and of COS-7 cells transfected with rat NT receptor cDNA, but at 104 higher doses than NT (8-13). However, TJN-950 was as effective as NT in inducing the fibrinolytic activity in bovine vascular aortic and human umbilical vein endothelial cells, and enhanced the migration of vascular endothelial cells. Moreover, administration of TJN-950 induced neovascularization in the rat cornea in vivo. TJN-950 had no effect on expression of uPA, plasminogen activator inhibitor-1 or uPA receptor mRNA. The binding of 125I-TJN-950 to cell membranes was blocked by unlabeled uPA and TJN-950, but not the amino-terminal or 12-32 fragment of uPA. TJN-950 may enhance uPA activity in vascular endothelial cells by interacting with the uPA receptor, resulting in induction of angiogenesis.

Original languageEnglish
Pages (from-to)341-345
Number of pages5
JournalFEBS Letters
Volume418
Issue number3
DOIs
Publication statusPublished - Dec 1 1997

All Science Journal Classification (ASJC) codes

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

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    Ushiro, S., Mizoguchi, K., Yoshida, S., Jimi, S. I., Fujiwara, T., Yoshida, M., Wei, E. T., Kitabgi, P., Amagaya, S., Ono, M., & Kuwano, M. (1997). Stimulation of cell-surface urokinase-type plasminogen activator and cell migration in vascular endothelial cells by a novel hexapeptide analogue of neurotensin. FEBS Letters, 418(3), 341-345. https://doi.org/10.1016/S0014-5793(97)01403-8