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

FEBS Letters
S UshiroM Kuwano

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 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 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.

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Citations

Mar 9, 2007·Inflammatory Bowel Diseases·Kara J Gross, Charalabos Pothoulakis
Nov 7, 2006·Neuropathology and Applied Neurobiology·S ServotteC Decaestecker
Oct 14, 2014·The American Journal of Pathology·Kyriaki BakirtziCharalabos Pothoulakis
Mar 15, 2005·American Journal of Physiology. Gastrointestinal and Liver Physiology·Paola BrunIgnazio Castagliuolo
Mar 13, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Genevieve E CampbellDiane M Duffy

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