Glomerular Basement Membrane Turnover in Young, Old, and Streptozotocin-Diabetic Rats

Abstract

Diabetic and senile glomerulosclerosis consists of thickening of the glomerular basement membranes (GBM) and augmentation of the mesangial matrix. The pathogenesis of these alterations is still controversial. Therefore, an in vivo study of the metabolism and the chemical composition of the GBM in streptozotocin-diabetic and old rats reported here was conducted: The turnover rate of the GBM, determined by the incorporation of labeled hydroxyproline, is prolonged in preparations from diabetic and aging rats. This can be explained by the decreased synthesis and delayed degradation of the GBM material found in both experimental groups. The biochemical analyses of the GBM revealed a higher content of hydroxylated amino acids, especially OH-lys, in the old and diabetic animals. The findings suggest that diabetic and senile glomerulosclerosis results from a prolonged turnover of the GBM and GBM-like material under the altered metabolic conditions investigated in this study.

Glomerular basement membrane synthesis and serum concentration of type IV collagen in streptozotocin-diabetic rats

“…However, the creatinine values were normal and Ilstrup et al [7] showed previously that diabetic rats did not display a lowered intravascular or extravascular volume when they had free access to water. An increased degradation of the basement membrane with a large release of 7S collagen or related structures is probably not responsible for the elevated levels, since the turnover of basement membranes is slowed down in diabetes [4,16]. A decrease in the disappearence rate of 7S collagen in diabetes which could lead to raised serum levels was not observed after injection of radiolabelled 7S collagen (D.Brocks, personal communication).…”

Basement membrane abnormalities in diabetes mellitus: Relationship to clinical microangiopathy

“…Studies of glomerular collagen metabolism in animals with experimentally induced diabetes have provided evidence that type IV collagen synthesis is i n c r e a~e d " ,~~,~~,~~~ and that degradation is impaired. 41, 219 In view of the importance of mesangial hypertrophy in the pathogenesis of diabetic nephropathy, and immunocytochemical evidence that the proportions of extracellular matrix components differ in mesangial matrix and basement membrane of glomerular capillaries, it is noteworthy that the glomerular basement membrane preparations utilized in the analyses discussed above and in other studies discussed below may differ in their content of mesangial matrix versus basement membrane for controls versus diabetics as well as between different l a b~r a t o r i e s .~~,~~~,~~~ In addition, purified basement membrane preparations may differ in their content (recovery) of lamina rara versus lamina densa macromolecules.76…”

Renoprotection From Diabetic Complications in OVE Transgenic Mice by Endothelial Cell Specific Overexpression of Metallothionein: A TEM Stereological Analysis

“…GBM thickening in diabetic human (Reddi, 1978) and a variety of animal models (Romen, 1980) has been thoroughly investigated, and though the precise metabolic processes by which basement membranes increase in width have not been clearly uncovered, a number of pathogenetic mechanisms are implicated, most of which include hyperglycemia-induced paradigms (Tsilibary, 2003)…”