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Stimulation of cell‐surface urokinase‐type plasminogen activator activity and cell migration in vascular endothelial cells by a novel hexapeptide analogue of neurotensin
Author(s) -
Ushiro Shin,
Mizoguchi Kazushige,
Yoshida Shigeo,
Jimi Sei-ichiro,
Fujiwara Tadami,
Yoshida Masaya,
Wei Edward T.,
Kitabgi Patrick,
Amagaya Sakae,
Ono Mayumi,
Kuwano Michihiko
Publication year - 1997
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(97)01403-8
Subject(s) - angiogenesis , plasminogen activator , endothelial stem cell , neurotensin , urokinase receptor , umbilical vein , urokinase , receptor , microbiology and biotechnology , chemistry , biology , endocrinology , in vitro , biochemistry , neuropeptide , cancer research , genetics
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 125 I‐NT to membranes of newborn rat brains and of COS‐7 cells transfected with rat NT receptor cDNA, but at 10 4 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 125 I‐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.