摘要
基质金属蛋白酶(MMPs)作为蛋白质水解酶,属于锌离子依赖的内肽酶家族,其几乎能够降解所有的细胞外基质(ECM)蛋白质成分。已知MMPs在许多的肾脏疾病中起到作用,如许多类型的肾小球肾炎和肾小管疾病,亦包括一些遗传性的肾脏疾病。从这方面,细胞外基质的累积被认为是发现糖尿病肾病的一个形态学特点,不仅与基质蛋白的过度合成有关,还与其被MMPs的降解减少有关。近些年,越来越多的证据表明,MMPs的活性表达与糖尿病肾病病人肾脏疾病,许多实验性动物模型之间存在显著关联。在这样的糖尿病环境下,MMPs的表达受到高浓度的葡萄糖、晚期的糖基化终产物(AGEs)、转化生长因子-β(TGF-β)、活化氧(ROS),转录因子及许多小分子核糖核酸的调节。在本综述中,我们关注与MMPs的结构和功能,以及他们在糖尿病肾病发病机制中的作用。
关键词: 糖尿病肾病,细胞外基质,金属蛋白酶,转化生长因子-β
Current Medicinal Chemistry
Title:A Glimpse of Matrix Metalloproteinases in Diabetic Nephropathy
Volume: 21 Issue: 28
Author(s): X. Xu, L. Xiao, P. Xiao, S. Yang, G. Chen, F. Liu, Y.S. Kanwar and L. Sun
Affiliation:
关键词: 糖尿病肾病,细胞外基质,金属蛋白酶,转化生长因子-β
摘要: Matrix metalloproteinases (MMPs) are proteolytic enzymes belonging to the family of zinc-dependent endopeptidases that are capable of degrading almost all the proteinaceous components of the extracellular matrix (ECM). It is known that MMPs play a role in a number of renal diseases, such as, various forms of glomerulonephritis and tubular diseases, including some of the inherited kidney diseases. In this regard, ECM accumulation is considered to be a hallmark morphologic finding of diabetic nephropathy, which not only is related to the excessive synthesis of matrix proteins, but also to their decreased degradation by the MMPs. In recent years, increasing evidence suggest that there is a good correlation between the activity or expression of MMPs and progression of renal disease in patients with diabetic nephropathy and in various experimental animal models. In such a diabetic milieu, the expression of MMPs is modulated by high glucose, advanced glycation end products (AGEs), TGF-β, reactive oxygen species (ROS), transcription factors and some of the microRNAs. In this review, we focused on the structure and functions of MMPs, and their role in the pathogenesis of diabetic nephropathy.
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Cite this article as:
Xu X., Xiao L., Xiao P., Yang S., Chen G., Liu F., Kanwar Y.S. and Sun L., A Glimpse of Matrix Metalloproteinases in Diabetic Nephropathy, Current Medicinal Chemistry 2014; 21 (28) . https://dx.doi.org/10.2174/0929867321666140716092052
DOI https://dx.doi.org/10.2174/0929867321666140716092052 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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