Delayed treatment with plasminogen activator inhibitor-1 decoys reduces tubulointerstitial fibrosis.

Abstract : We examined the capacity of delayed inhibition of plasminogen activator inhibitor-1 (PAI-1) to reduce tubulointerstitial fibrosis induced by unilateral ureteral obstruction (UUO) in mice. Small peptides mimicking parts of urokinase (uPA) and tissular plasminogen activator (tPA) and serving as decoy molecules for PAI-1 were administered daily during the late stages (3 to 8 days) of UUO. Treatment with PAI-1 decoys reduced interstitial deposition of fibronectin, collagen III and collagen IV without changes in macrophage and myofibroblast infiltration. Interestingly, while PAI-1 activity was reduced and the combined uPA and tPA activity was increased, the antifibrotic effect was obtained without modification of plasmin activity but with increased of hepatocyte growth factor (HGF) expression. We show for the first time that treatment with small PAI-1 decoy peptides reduces established tubulointerstitial fibrosis. This protective effect probably resulted from increased degradation of the extracellular matrix by an HGF dependent mechanism.
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Experimental biology and medicine (Maywood, N.J.), 2009, 234 (12), pp.1511-8. 〈10.3181/0903-RM-105〉
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Contributeur : Marie Francoise Simon <>
Soumis le : mercredi 5 mai 2010 - 11:55:12
Dernière modification le : jeudi 13 septembre 2018 - 10:26:05

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Julien Gonzalez, Julie Klein, Sharmila Chauhan, Eric Neau, Denis Calise, et al.. Delayed treatment with plasminogen activator inhibitor-1 decoys reduces tubulointerstitial fibrosis.. Experimental biology and medicine (Maywood, N.J.), 2009, 234 (12), pp.1511-8. 〈10.3181/0903-RM-105〉. 〈inserm-00480896〉

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