Ischemia-reperfusion injury stimulates gelatinase expression and activity in kidney glomeruli

被引:32
作者
Caron, A [1 ]
Desrosiers, RR [1 ]
Langlois, S [1 ]
Béliveau, R [1 ]
机构
[1] Univ Quebec, Hop St Justine, Ctr Cancerol Charles Bruneau, Mol Med Lab, Montreal, PQ H3C 3P8, Canada
关键词
gelatinases; ischemia; reperfusion; TIMPs; ZO-1; CD-44; LRP; glomeruli;
D O I
10.1139/Y05-011
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Although ischemia remains the leading cause of acute renal failure in humans, there is little information on the expression and activities of gelatinases of kidney glomeruli during ischemia-reperfusion injury. In this study, we used a unilateral ischemia-reperfusion model to investigate the activity and expression of gelatinases in glomeruli during acute ischemia. Unilateral ischemia was induced in rats by vascular clamping (30 min) followed by reperfusion (60 min) and isolation of glomeruli. The activity and expression of gelatinase proteins were determined by gelatin zymography and Western blotting. Gelatinase mRNA levels were evaluated by reverse transciptase-PCR. Ischemia and reperfusion increased serum creatinine levels, hallmark of acute renal failure. Ischemia induced mRNA and protein MMP-2 expression. There was strong stimulation of MMP-9 mRNA, both forms of dimeric MMP-9, and active mono meric MMP-9. In contrast to TIMP-1 decreasing, TIMP-2 protein and mRNA increased during ischemia. During reperfusion, there was a gradual reversal of the MMP-2 and MMP-9 levels and a strong inhibition of TIMP-1 and TIMP-2 at the protein and mRNA levels. Endocytic receptor LRP was increased during ischemia and returned to normal during reperfusion. Expression of MMP-9 docking receptor CD-44 was increased during reperfusion. Finally, ZO-1, an in vivo MMP-9 substrate, was degraded during ischemia, revealing that MMP-9 upregulated during ischemia was functional. Our data suggest that stimulation of gelatinase activity during ischemia could contribute to glomeruli injury, providing new therapeutic targets for acute renal failure in humans. In contrast, elevated monomeric MMP-9 activity due to TIMP-1 decrease during reperfusion may participate to glomerular recovery.
引用
收藏
页码:287 / 300
页数:14
相关论文
共 60 条
  • [1] Effects of matrix metalloproteinase-9 gene knock-out on the proteolysis of blood-brain barrier and white matter components after cerebral ischemia
    Asahi, M
    Wang, XY
    Mori, T
    Sumii, T
    Jung, JC
    Moskowitz, MA
    Fini, ME
    Lo, EH
    [J]. JOURNAL OF NEUROSCIENCE, 2001, 21 (19) : 7724 - 7732
  • [2] Cellular and molecular predictors of chronic renal dysfunction after initial ischemia/reperfusion injury of a single kidney
    Azuma, H
    Nadeau, K
    Takada, M
    Mackenzie, HS
    Tilney, NL
    [J]. TRANSPLANTATION, 1997, 64 (02) : 190 - 197
  • [3] Extracellular matrix-related genes in kidney after ischemic injury:: potential role for TGF-β in repair
    Basile, DP
    Martin, DR
    Hammerman, MR
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY, 1998, 275 (06) : F894 - F903
  • [4] Booth A G, 1974, Biochem J, V142, P575
  • [5] Tissue inhibitors of metalloproteinases: evolution, structure and function
    Brew, K
    Dinakarpandian, D
    Nagase, H
    [J]. BIOCHIMICA ET BIOPHYSICA ACTA-PROTEIN STRUCTURE AND MOLECULAR ENZYMOLOGY, 2000, 1477 (1-2): : 267 - 283
  • [6] EFFECT OF REVERSIBLE ATP DEPLETION ON TIGHT-JUNCTION INTEGRITY IN LLC-PK1 CELLS
    CANFIELD, PE
    GEERDES, AM
    MOLITORIS, BA
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY, 1991, 261 (06): : F1038 - F1045
  • [7] Kidney ischemia-reperfusion regulates expression and distribution of tubulin subunits, β-actin and rho GTPases in proximal tubules
    Caron, A
    Desrosiers, RR
    Béliveau, R
    [J]. ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 2004, 431 (01) : 31 - 46
  • [8] CAWSTON T, 1998, MOL MED TODAY, V272, P33175
  • [9] Matrix metalloproteinase-2 contributes to ischemia-reperfusion injury in the heart
    Cheung, PY
    Sawicki, G
    Wozniak, M
    Wang, WJ
    Radomski, MW
    Schulz, R
    [J]. CIRCULATION, 2000, 101 (15) : 1833 - 1839
  • [10] Modulation of Rho and cytoskeletal protein attachment to membranes by a prenylcysteine analog
    Desrosiers, RR
    Gauthier, F
    Lanthier, J
    Béliveau, R
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (20) : 14949 - 14957