There is much evidence that basement membranes, such as in the renal glomerulus, act as macromolecular sieves, restricting the passage of proteins. Cross-linking of matrix proteins, as occurs because of advanced glycosylation end products (AGEs) in diabetes, may have an effect on the sieving properties of the basement membrane. To test this hypothesis, Matrigel, a basement membrane-like matrix, was cross-linked with glycolaldehyde and control and cross-linked matrices compared. Control matrices allowed less bovine serum albumin to pass through than did cross-linked matrices, with sieving coefficients (SCs) of 0.38 ± 0.02 and 0.52 ± 0.02, respectively (P < 0.0005). The control matrices also allowed less cross-linked albumin through than did the cross-linked matrices: 0.13 ± 0.01 vs. 0.17 ± 0.02 (P < 0.002). The SCs of a series of fluorescein isothiocyanate dextrans (four sizes, Mr 16,000–168,000) were lower for the control matrix than for the cross-linked matrix (P < 0.03). In addition, the SC for glycated albumin (incubated with glucose-6-phosphate) was higher than that of normal albumin for both the control (P < 0.04) and cross-linked matrices (P < 0.001). These data indicate that cross-linking of the matrix increases permeability to macromolecules. Analysis of the data using fiber-matrix theory suggests that the mean fiber radius was increased in the cross-linked matrix. The data also indicate that glycated albumin filters through the matrices more easily than does normal albumin. In relation to the situation seen in vivo, it is possible that glycation of circulating proteins and AGE modification of glomerular basement membrane proteins may both contribute to the proteinuria seen in diabetes.
Skip Nav Destination
Article navigation
Original Articles|
March 01 1996
Effect of Cross-Linking on Matrix Permeability: A Model for AGE-Modified Basement Membranes
Judy Boyd-White;
Judy Boyd-White
Molecular and Cellular Pathobiology Program Medical University of South Carolina
South Carolina
Search for other works by this author on:
James C Williams, Jr
James C Williams, Jr
Department of Anatomy Indiana University School of Medicine, Indianapolis
Indiana
Search for other works by this author on:
Address correspondence and reprint requests to Dr. Judy Boyd-White, Department of Anatomy, MS 221, Indiana University School of Medicine, 635 Barnhill Dr., Indianapolis, IN 46202.
Diabetes 1996;45(3):348–353
Article history
Received:
March 14 1995
Revision Received:
October 26 1995
Accepted:
October 26 1995
PubMed:
8593941
Citation
Judy Boyd-White, James C Williams; Effect of Cross-Linking on Matrix Permeability: A Model for AGE-Modified Basement Membranes. Diabetes 1 March 1996; 45 (3): 348–353. https://doi.org/10.2337/diab.45.3.348
Download citation file:
91
Views