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  • Transglutaminase-mediated stiffening of the glomerular basement membrane mitigates pressure-induced reductions in molecular sieving coefficient by reducing compression
Title: Transglutaminase-mediated stiffening of the glomerular basement membrane mitigates pressure-induced reductions in molecular sieving coefficient by reducing compression
Proteinuria, the presence of high molecular weight proteins in the urine, is a primary indicator of chronic kidney disease. Proteinuria results from increased molecular permeability of the glomerular filtration barrier combined with saturation or defects in tubular protein reabsorption. Any solute that passes into the glomerular filtrate traverses the glomerular endothelium, the glomerular basement membrane, and the podocyte slit diaphragm. Damage to any layer of the filter has reciprocal effects on other layers to increase glomerular permeability. The GBM is thought to act as a compressible ultrafilter that has increased molecular selectivity with increased pressure due to compression that reduced the porosity of the GBM with increased pressure. In multiple forms of chronic kidney disease, crosslinking enzymes are upregulated and may act to increase GBM stiffness. Here we show that enzymatically crosslinking porcine GBM with transglutaminase increases the stiffness of the GBM and mitigates pressure-dependent reductions in molecular sieving coefficient. This was modeled mathematically using a modified membrane transport model accounting for GBM compression. Changes in the mechanical properties of the GBM may contribute to proteinuria through pressure-dependent effects on GBM porosity.  more » « less
Award ID(s):
2216394
PAR ID:
10516603
Author(s) / Creator(s):
;
Publisher / Repository:
Elsevier
Date Published:
Journal Name:
Matrix Biology
Volume:
130
Issue:
C
ISSN:
0945-053X
Page Range / eLocation ID:
47 to 55
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
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