4.6 Article

A Glimpse of Matrix Metalloproteinases in Diabetic Nephropathy

Journal

CURRENT MEDICINAL CHEMISTRY
Volume 21, Issue 28, Pages 3244-3260

Publisher

BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/0929867321666140716092052

Keywords

Diabetic nephropathy; extracellular matrix; metalloproteinases; TGF-beta

Funding

  1. Creative Research Group Fund of the National Foundation Committee of Natural Sciences of China [81270812, 81370832]
  2. Doctoral Fund of Ministry of Education of China [20110162110012]
  3. Furong Scholars Fund from Hunan Province Education Department
  4. Program for Changjiang Scholars and Innovative Research Team in University [IRT1195]
  5. National Institutes of Health [DK-60635]

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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-beta, 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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