Accumulation of worn-out GBM material substantially contributes to mesangial matrix expansion in diabetic nephropathy.

Accumulation of worn-out GBM material substantially contributes to mesangial matrix expansion in diabetic nephropathy. Am J Physiol Renal Physiol. 2017 Feb 22;:ajprenal.00020.2017 Authors: Kriz W, Löwen J, Federico G, van den Born J, Gröne E, Gröne HJ Abstract Thickening of the glomerular basement membrane (GBM) and expansion of the mesangial matrix are hallmarks of diabetic nephropathy (DN) generally considered to emerge from different sites of overproduction; GBM components from podocytes and mesangial matrix from mesangial cells. Re-evaluation of 918 biopsies with DN revealed strong evidence that these mechanisms are connected to each other, wherein excess GBM components fail to undergo degradation and are deposited in the mesangium. These data do not exclude that also mesangial cells synthesize components that contribute to the accumulation of matrix in the mesangium. Light, electron microscopic, immunofluorescence and in-situ hybridization studies clearly show that the thickening of the GBM is not only due to overproduction of components of the mature GBM (α3 and α5 chains of collagen IV and agrin) by podocytes, but also to resumed increased synthesis of the α1 chain of collagen IV and of perlecan by endothelial cells usually seen during embryonic development. We hypothesize that these abnormal production mechanisms are caused by different processes; overproduction of mature GBM-components by the diabetic milieu and regres...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research