Absence of Gelatinase (MMP-9) or Collagenase (MMP-13) Attenuates Adriamycin-Induced Albuminuria and Glomerulosclerosis
Absence of Gelatinase (MMP-9) or Collagenase (MMP-13) Attenuates Adriamycin-Induced Albuminuria and Glomerulosclerosis
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DOI：
10.1159/000312883
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发表时间：
2010-01-01
影响因子：
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通讯作者：
Itoh, Hiroshi
中科院分区：
文献类型：
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作者：
Sakamaki, Yusuke;Sasamura, Hiroyuki;Itoh, Hiroshi
背景/目的：基质金属蛋白酶（MMPs）在肾小球损伤的发病机制中的作用似乎是复杂的。为了研究单个基质金属蛋白酶的作用，我们研究了阿霉素诱导的蛋白尿和肾小球硬化症的过程中缺乏明胶酶（MMP-9）或胶原酶（MMP-13）的小鼠。方法：阿霉素给予MMP-9或MMP-13敲除（KO）小鼠。通过定量白蛋白尿、肾小球损伤评分和IV型胶原免疫染色来评估肾小球损伤。导致明显的蛋白尿和肾小球硬化，在4-8周达到高峰。与对照相比，MMP-9 KO和MMP-13 KO小鼠中的蛋白尿和肾小球硬化显著减弱（p < 0.05）。与此相反，治疗野生型小鼠与广谱MMP抑制剂强力霉素没有一个有益的影响蛋白尿和glomerulosclerosis.Conclusion：这些结果支持明胶酶（MMP-9）和胶原酶（MMP-13）在阿霉素诱导的肾小球硬化模型肾小球损伤的发病机制中的作用。对MMP-9和/或MMP-13具有高度特异性的MMP抑制剂可能是提供更有效的治疗以抑制肾小球硬化症发展的潜在未来候选物。版权所有（C）2010 S. Karger AG，巴塞尔
Background/Aims: The role of matrix metalloproteinases (MMPs) in the pathogenesis of glomerular injury appears to be complex. To investigate the role of individual MMPs, we examined the course of Adriamycin-induced albuminuria and glomerulosclerosis in mice lacking either a gelatinase (MMP-9) or a collagenase (MMP-13).Methods: Adriamycin was administered to MMP-9 or MMP-13 knockout (KO) mice. Glomerular injury was assessed by the quantification of albuminuria, the glomerular injury score and type IV collagen immunostaining.Results: Treatment of mice with Adriamycin (18 mg/kg i.v.) resulted in marked albuminuria and glomerulosclerosis reaching a peak at 4-8 weeks. The albuminuria and glomerulosclerosis were significantly (p < 0.05) attenuated in both the MMP-9 KO and MMP-13 KO mice compared to controls. In contrast, treatment of wild-type mice with the broad-spectrum MMP inhibitor doxycycline did not have a beneficial effect on the albuminuria and glomerulosclerosis.Conclusion: These results support a role for both gelatinase (MMP-9) and collagenase (MMP-13) in the pathogenesis of glomerular injury in the Adriamycin-induced glomerulosclerosis model. MMP inhibitors with high specificity towards MMP-9 and/or MMP-13 may be potential future candidates to provide more effective therapies to inhibit the development of glomerulosclerosis. Copyright (C) 2010 S. Karger AG, Basel