Journal Article

Diabetic nephropathy: molecular analysis of extracellular matrix and clinical studies update

Gary E. Striker, Richard D. Eastman and Liliane J. Striker

in Nephrology Dialysis Transplantation

Published on behalf of European Renal Association - European Dialysis and Transplant Assoc

Volume 11, issue supp5, pages 58-61
Published in print January 1996 | ISSN: 0931-0509
e-ISSN: 1460-2385 | DOI: http://dx.doi.org/10.1093/ndt/11.supp5.58
Diabetic nephropathy: molecular analysis of extracellular matrix and clinical studies update

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Background

Progressive glomerulosclerosis associated with decreasing kidney function, resulting in end-stage renal failure, is the major finding in diabetic nephropathy. There are multiple components of the extracellular matrix, and neither the exact composition nor the factors responsible for its increase in diabetic nephropathy is known.

Methods

We examined matrix synthesis and degradation at the level of gene expression and ECM composition, in the glomeruli of diabetic mice transgenic for a mutated bGH and their littermate controls, and in renal biopsies of patients with diabetic nephropathy.

Results

We found that streptozotocin-treated C57BL/SJL mice developed histological lesions closely resembling human diabetic glomerulosclerosis, whereas there were no glomerular lesions in diabetic mice transgenic for a growth hormone analogue which competes with native GH and results in dwarfism. We found that diabetic glomerulosclerosis in mice was associated with an increase in type IV collagen and laminin synthesis, and that these changes are selectively inhibited in dwarf mice transgenic for the mutant GH analogue. Preliminary examination of glomeruli isolated from renal biopsies revealed a homogeneous elevation in the α2/α3IV ratio among diabetics.

Conclusions

These data suggested that diabetic nephropathy is characterized by modifications in ECM gene regulation in both mouse models and in diabetics, and that GH may promote the susceptibility to this complication. Finally, the data from the Diabetes Control and Complications Trial is updated, emphasizing the importance of close glucose control in the amelioration of an elevated albumin excretion rate as a continuous function of the level of control.

Keywords: diabetes mellitus; extracellular matrix; glomerulosclerosis; molecular analysis

Journal Article.  0 words. 

Subjects: Nephrology

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