Ischemia injury alters endothelial cell properties of kidney cortex: stimulation of MMP-9.

Abstract

Although ischemia is the leading cause of acute renal failure in human, there is little information on the remodeling the kidney endothelium matrix during ischemic injury. In this study, we investigated the activity and expression of MMP-2 and MMP-9, in an isolated endothelial fraction following an acute in vivo reversible ischemia induced in rats by vascular clamping. Ischemia increased serum creatinine levels 1.4-fold, hallmark of acute renal failure. Isolation of the endothelial cell fraction was performed by affinity chromatography using an anti-PECAM-1 antibody. The isolated fraction was assessed by Western blotting analysis of endothelial cell markers. The positively selected fractions were enriched in the endothelial markers eNOS and PECAM-1 by 128-fold and 44-fold, respectively. Gelatin zymography showed that ischemia strongly stimulated proteolytic activity of proMMP-2 (1.8-fold), proMMP-9 (3-fold) and MMP-9 (4-fold) in the endothelial fractions. Western blot analysis indicated that TIMP-2 protein level increased by 3.2-fold in the endothelial fractions during ischemia. Surprisingly, TIMP-1 was absent from the endothelial preparations but was easily detected in the non-endothelial cells. Levels of the endocytic receptor LRP were increased by 2-fold during ischemia in the endothelial fractions. Occludin, a known in vivo MMP-9 substrate, was partly degraded in the endothelial fractions during ischemia, suggesting that the MMP-9 which was upregulated during ischemia was functional. These data suggest that ischemia in kidney could lead to the degradation of the vascular basement membrane and to increased permeability. This suggests new therapeutic approaches for ischemic pathologies by targeting MMP-9 and its regulators.

• Authors: Annick Caron, Richard R Desrosiers, Richard Béliveau
• Journal: Experimental cell research (Exp Cell Res) Vol. 310 Issue 1 Pg. 105-16 (Oct 15 2005) ISSN: 0014-4827 [Print] United States
• PMID: 16112109 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Membrane Proteins
• OCLN protein, human
• Occludin
• Ocln protein, rat
• Platelet Endothelial Cell Adhesion Molecule-1
• Tissue Inhibitor of Metalloproteinase-1
• Tissue Inhibitor of Metalloproteinase-2
• Creatinine
• Nitric Oxide Synthase
• Nitric Oxide Synthase Type III
• Nos3 protein, rat
• Leukocyte Common Antigens
• Plasminogen Activators
• Matrix Metalloproteinase 9

Topics

• Acute Kidney Injury (pathology)
• Animals
• Creatinine (blood)
• Endothelial Cells (metabolism, pathology)
• Ischemia (enzymology)
• Kidney Cortex (metabolism, pathology)
• Leukocyte Common Antigens (metabolism)
• Male
• Matrix Metalloproteinase 9 (biosynthesis, physiology)
• Membrane Proteins (metabolism)
• Nitric Oxide Synthase (metabolism)
• Nitric Oxide Synthase Type III
• Occludin
• Plasminogen Activators (biosynthesis)
• Platelet Endothelial Cell Adhesion Molecule-1 (metabolism)
• Rats
• Rats, Sprague-Dawley
• Tissue Inhibitor of Metalloproteinase-1 (metabolism)
• Tissue Inhibitor of Metalloproteinase-2 (metabolism)