The sulfilimine cross-link of collagen IV contributes to kidney tubular basement membrane stiffness.

Bhave G, Colon S, Ferrell N
Am J Physiol Renal Physiol. 2017 313 (3): F596-F602

PMID: 28424209 · PMCID: PMC5625101 · DOI:10.1152/ajprenal.00096.2017

Basement membranes (BMs), a specialized form of extracellular matrix, underlie nearly all cell layers and provide structural support for tissues and interact with cell surface receptors to determine cell behavior. Both macromolecular composition and stiffness of the BM influence cell-BM interactions. Collagen IV is a major constituent of the BM that forms an extensively cross-linked oligomeric network. Its deficiency leads to BM mechanical instability, as observed with glomerular BM in Alport syndrome. These findings have led to the hypothesis that collagen IV and its cross-links determine BM stiffness. A sulfilimine bond (S = N) between a methionine sulfur and a lysine nitrogen cross-links collagen IV and is formed by the matrix enzyme peroxidasin. In peroxidasin knockout mice with reduced collagen IV sulfilimine cross-links, we find a reduction in renal tubular BM stiffness. Thus this work provides the first direct experimental evidence that collagen IV sulfilimine cross-links contribute to BM mechanical properties and provides a foundation for future work on the relationship of BM mechanics to cell function in renal disease.

Copyright © 2017 the American Physiological Society.

MeSH Terms (16)

Animals Basement Membrane Biomechanical Phenomena Collagen Type IV Cross-Linking Reagents Elastic Modulus Extracellular Matrix Proteins Genotype Imines Kidney Mice, Inbred C57BL Mice, Knockout Peroxidase Phenotype Protein Conformation Tensile Strength

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