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

摘要: Thickening of the glomerular basement membrane (GBM) and expansion mesangial matrix are hallmarks diabetic nephropathy (DN), generally considered to emerge from different sites overproduction: GBM components podocytes cells. Reevaluation 918 biopsies with DN revealed strong evidence that these mechanisms connected each other, wherein excess fail undergo degradation deposited in mesangium. These data do not exclude cells also synthesize contribute accumulation Light, electron microscopic, immunofluorescence, situ hybridization studies clearly show thickening is due only overproduction mature (α3 α5 chains collagen IV agrin) by but resumed increased synthesis α1 chain perlecan endothelial usually seen during embryonic development. We hypothesize abnormal production caused processes: GBM-components milieu regression an mode decreased availability mediators podocytes.