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Diabetic Complications

Scope of this initiative within the CMB:

Diabetes has become a world epidemic with almost 180 million people affected. Overtime, diabetes results in the progressive development of such complications as nephropathy, retinopathy, neurodegenerative diseases, and atherosclerosis. How hyperglycemia of diabetes causes diabetic complications is poorly understood. Major hypothesis include increased activation of cytokines, activation of protein kinase C, increased formation of reactive oxygen species, activation of the aldose reductase pathway, and increased modification of proteins by glucose and its derivatives.

Diabetic nephropathy is one of the most frequent and severe complications of diabetes. It is characterized by the expansion of mesangial matrix, thickening of glomerular basement membrane, and by podocyte effacement, leading to the gradual loss of kidney filtration function and to the end stage renal disease. Mechanistically, these morphological and physiological changes are thought to be caused by several factors. One is a TGFb-dependent upregulation of collagen type IV, a major component of glomerular matrices. Another factor is a glucose-induced chemical modification of collagen IV, laminins, and other matrix components, which decrease their susceptibility to matrix metalloproteinases. These chemical modifications may also interfere with integrin signaling and integrin-dependent cell-matrix interactions. Understanding matrix remodeling process and modifications of matrix proteins in diabetes provide guidelines for development of novel therapeutic treatments for diabetic nephropathy.

The Center for Matrix biology promotes the exchange of information between Vanderbilt researchers interested in understanding the mechanisms of diabetic nephropathy and other diabetic complications and development of preventive therapies.

  Members (14)

Borza, Dorin-Bogdan
Chetyrkin, Sergei
Davidson, Jeffrey M.
Hanks, Steven K.
Hudson, Billy G.
Moeckel, Gilbert
Pedchenko, Vadim
Voziyan, Paul
Zent, Roy

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