Title: Tissue-type plasminogen activator modulates inflammatory responses and renal function in ischemia reperfusion injury
Authors: Roelofs, Joris J. T. H ×
Rouschop, Kasper M. A
Leemans, Jaklien C
Claessen, Nike
de Boer, Anita M
Frederiks, Wilma M
Lijnen, Roger
Weening, Jan J
Florquin, Sandrine #
Issue Date: Jan-2006
Series Title: Journal of the American Society of Nephrology vol:17 issue:1 pages:131-140
Conference: date:Univ Amsterdam, Acad Med Ctr, Dept Pathol, NL-1105 AZ Amsterdam, Netherlands; Univ Amsterdam, Acad Med Ctr, Dept Expt Internal Med, NL-1105 AZ Amsterdam, Netherlands; Univ Amsterdam, Acad Med Ctr, Dept Cell Biol & Histol, NL-1105 AZ Amsterdam, Netherlands; Katholieke Univ Leuven, Ctr Mol & Vasc Biol, Louvain, Belgium
Abstract: Acute renal failure is often the result of ischemia-reperfusion (I/R) injury. Neutrophil influx is an important damaging event in I/R. Tissue-type plasminogen activator (tPA) not only is a major fibrinolytic agent but also is involved in inflammatory processes. A distinct upregulation of tPA after I/R, with de novo tPA production by proximal renal tubules, was found. For investigating the role of tPA in I/R, renal ischemia was induced in tPA-/- and wild-type (WT) mice by clamping both renal arteries for 35 min followed by reperfusion. Mice were killed 1, 5, and 10 d after reperfusion. After 1 d, tPA-/- mice displayed significantly less neutrophil influx into the interstitial area compared with WT mice. In addition, tPA-/- mice showed quicker recovery of renal function than WT mice. The protocol was repeated after injection of tPA-antisense oligonucleotides into WT mice, leading to even more explicit results: Antisense-treated mice showed less histologic damage, better renal function, and less neutrophil influx than control mice. Surprising, complement C3 concentration, levels of proinflammatory cytokines and chemokines, intercellular adhesion molecule-1 expression, and matrix metalloproteinase activity were similar in WT and tPA-/- mice. Plasmin activity levels in WT and tPA-/- kidneys were also comparable, indicating that tPA influences neutrophil influx into ischemic renal tissue independent from plasmin generation. This study shows that targeting tPA could be of therapeutic importance in treating I/R injury by diminishing neutrophil influx and preserving renal function.
ISSN: 1046-6673
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Molecular and Vascular Biology
× corresponding author
# (joint) last author

Files in This Item:

There are no files associated with this item.

Request a copy


All items in Lirias are protected by copyright, with all rights reserved.

© Web of science