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首页> 外文期刊>Canadian Journal of Physiology and Pharmacology >Ischemia–reperfusion injury stimulates gelatinase expression and activity in kidney glomeruli.
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Ischemia–reperfusion injury stimulates gelatinase expression and activity in kidney glomeruli.

机译：缺血再灌注损伤会刺激肾小球中明胶酶的表达和活性。

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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.
机译：尽管缺血仍然是人类急性肾衰竭的主要原因，但关于缺血再灌注损伤期间肾小球明胶酶表达和活性的信息很少。在这项研究中，我们使用单侧缺血-再灌注模型研究急性缺血期间肾小球中明胶酶的活性和表达。通过血管钳夹（30分钟），再灌注（60分钟）和肾小球分离来诱导大鼠单侧缺血。通过明胶酶谱和Western印迹法测定明胶酶蛋白的活性和表达。通过逆转录酶-PCR评估明胶酶mRNA水平。缺血和再灌注增加血清肌酐水平，这是急性肾衰竭的标志。缺血诱导mRNA和蛋白MMP-2表达。 MMP-9 mRNA有很强的刺激性，既有二聚体MMP-9形式，又有活性单体MMP-9形式。与TIMP-1减少相反，TIMP-2蛋白和mRNA在缺血期间增加。在再灌注过程中，MMP-2和MMP-9的水平逐渐反转，并且在蛋白质和mRNA水平上对TIMP-1和TIMP-2产生了强烈的抑制作用。内吞受体LRP在缺血期间增加，在再灌注期间恢复正常。在再灌注过程中，MMP-9对接受体CD-44的表达增加。最后，ZO-1，一种体内MMP-9底物，在缺血过程中被降解，表明在缺血过程中上调的MMP-9具有功能。我们的数据表明，缺血过程中明胶酶活性的刺激可能导致肾小球损伤，为人类急性肾衰竭提供了新的治疗靶点。相反，由于再灌注过程中TIMP-1减少，单体MMP-9活性升高可能参与了肾小球的恢复。

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