EXTRACELLULAR MATRIX GLYCATION, REDOX STATUS AND CROSS-LINKING

Extracellular matrix (ECM) is mostly comprised of proteins and proteoglycans, which form supramolecular assemblies. It provides shape and mechanical properties - mediated by covalent cross-links - to tissues and organs, and regulates cell behavior. Covalent cross-linking of the ECM is mediated by transglutaminase-2, glycation and more specifically by enzymes of the lysyl oxidase family. Lysyl oxidase, or protein-lysine 6-oxidase, contains the redox cofactor lysyl-tyrosine quinone and is a source of hydrogen peroxide, a reactive oxygen species. We have investigated ECM cross-links formed via glycation and lysyl oxidase in liver and skin fibrosis and we are currently building the interaction network of lysyl oxidase to determine if it plays further biological roles in ECM and in pericellular matrix at the cell surface.