Dysregulation of renal MMP-3 and MMP-7 in canine X-linked Alport syndrome.
Dysregulation of renal MMP-3 and MMP-7 in canine X-linked Alport syndrome.
复制标题
犬 X 连锁 Alport 综合征中肾 MMP-3 和 MMP-7 的失调。
DOI：
10.1007/s00467-004-1805-5
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Cosgrove,Dominic
中科院分区：
文献类型：
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作者：
Rao,VelidiH;Lees,GeorgeE;Kashtan,CliffordE;Delimont,DuaneC;Singh,Rakesh;Meehan,DanielT;Bhattacharya,Gautam;Berridge,BrianR;Cosgrove,Dominic
基质金属蛋白酶（matrix metalloproteinases，MMPs）在许多生物学和病理学过程中起重要的调节作用，但其在Alport综合征（Alport syndrome，AS）中的具体作用尚不清楚。在这项研究中，自然发生的犬X连锁AS被用来证明MMP-3和MMP-7在Alport肾脏发病机制中的潜在作用。最近，我们证明了MMP-2，MMP-9和MMP-14的表达上调，在狗的肾皮质与自发形式的XLAS。在本研究中，我们检查了正常和XLAS犬的肾皮质尸检样本中的MMP-3和MMP-7，因为它们具有激活MMP-2和MMP-9的潜力。免疫组织化学分析显示，MMP-3和MMP-7在XLAS肾间质中有很强的免疫染色，而在正常犬的类似区域中几乎没有观察到免疫染色。RT-PCR和酪蛋白酶谱分析证实，MMP-3和MMP-7的mRNA转录和活性在XLAS肾中均升高。这些MMP的诱导可能有助于与纤维化过程相关的组织破坏，同时在XLAS中增加MMP-3和MMP-7对MMP-2和MMP-9的激活。因此，这些数据进一步暗示了基质金属蛋白酶在与AS相关的进行性肾脏发病机制中的作用。
Matrix metalloproteinases (MMPs) play an important regulatory role in many biological and pathological processes and their specific role in Alport syndrome (AS) is not yet clearly defined. In this study, the naturally occurring canine X-linked AS was used to demonstrate a potential role for MMP-3 and MMP-7 in Alport renal pathogenesis. Recently, we demonstrated that the expression of MMP-2, MMP-9 and MMP-14 was upregulated in the renal cortex of dogs with a spontaneous form of XLAS. In the present study, we examined necropsy samples of renal cortex from normal and XLAS dogs for MMP-3 and MMP-7 as they have the potential to activate MMP-2 and MMP-9. Immunohistochemical analysis showed strong immunostaining for both MMP-3 and MMP-7 in the interstitial space of XLAS kidneys, while virtually no immunostaining was observed in similar fields from normal dogs. RT-PCR and casein zymography confirmed that both mRNA transcripts and activities of MMP-3 and MMP-7 are elevated in XLAS kidneys. The induction of these MMPs likely contributes to tissue destruction associated with the fibrogenic process, while augmenting the activation of MMP-2 and MMP-9 by MMP-3 and MMP-7 in XLAS. Thus, these data further implicate a role for the MMPs in progressive renal pathogenesis associated with AS.