REVIEW: Role of Matrix Metalloproteinases in Development of Diabetic Nephropathy

P. Z. Khasigov^*, S. A. Ktzoeva, T. M. Gatagonova, I. E. Tareeva, S. V. Grachev, and T. T. Berezov

Sechenov Moscow Medical Academy, Bol'shaya Pirogovskaya ul. 2/6, Moscow, 119881 Russia; fax: (095) 248-0181

^* To whom correspondence should be addressed.

Received November 10, 1999; Revision received December 9, 1999

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This review considers molecular mechanisms that underlie disorders in the structure and metabolism of renal extracellular matrix in diabetic nephropathy. The contribution of the increased synthesis of renal extracellular matrix proteins in the accumulation of renal mesangial matrix is considered, and the important role of the degradation system of the extracellular matrix proteins in the development of fibrosis is also shown. Data on changes in mRNA expression for the matrix metalloproteinases (MMP) and tissue inhibitors of metalloproteinases (TIMP) in various forms of diabetic nephropathy are presented. A correlation is established between changes in the balance of MMP proteolytic activity and TIMP activity and the accumulation of extracellular matrix.

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KEY WORDS: extracellular matrix, glomerular basement membranes, tubular basement membrane, matrix metalloproteinases, tissue metalloproteinase inhibitors, diabetic nephropathy

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