Date of Award

1992

Embargo Period

8-1-2024

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Cell Biology and Anatomy

College

College of Graduate Studies

First Advisor

James C. Williams, Jr.

Second Advisor

Greg J. Cole

Third Advisor

Florence Hutchison

Fourth Advisor

Richard V. Paul

Fifth Advisor

Eric R. Lacy

Abstract

Although basement membranes are ubiquitous structures throughout the body, basement membranes have distinct compositions that are specific to their location. This basement membrane heterogeneity may, in part, reflect functional differences among various basement membranes. We examined basement membrane heterogeneity in normal, healthy mouse kidneys to assess the similarities and differences between glomerular and tubular basement membrane composition. It was demonstrated that mouse glomerular and tubular basement membrane share similar compositions but differ with respect to specific amounts of some components. In diabetes mellitus and passive Heymann nephritis (PHN), damage to the glomerular barrier occurs and is accompanied by an increase in permeability to proteins the size of albumin and larger: Presumably, the biochemical nature of the filter is not maintained. The acute effects of streptozotocin diabetes and PHN on the macromolecular composition of rat GBM was investigated to determine if changes in composition correlated with proteinuria in these two models of kidney disease. Diabetes and PHN were shown to have differential effects on GBM composition during the establishment of proteinuria. Diabetes affected the GBM macromolecular composition; a significant reduction in anionic charge content correlated with significant proteinuria and significant increases in both laminin and fibronectin that occurred during the period immediately following proteinuria. However, PHN had no effect on the GBM macromolecular composition despite overt proteinuria after five days. These results suggest that the stimuli that lead to changes in GBM composition in diabetes are likely related to those which result in proteinuria; however, there appears to be no relationship between the GBM composition and overt proteinuria in PHN, or the mechanisms for the induction of proteinuria between diabetes and PHN.

Rights

All rights reserved. Copyright is held by the author.

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