title: Proteases decode the extracellular matrix cryptome.
abstract: The extracellular matrix is comprised of 1100 core-matrisome and matrisome-associated proteins and of glycosaminoglycans. This structural scaffold contributes to the organization and mechanical properties of tissues and modulates cell behavior. The extracellular matrix is dynamic and undergoes constant remodeling, which leads to diseases if uncontrolled. Bioactive fragments, called matricryptins, are released from the extracellular proteins by limited proteolysis and have biological activities on their own. They regulate numerous physiological and pathological processes such as angiogenesis, cancer, diabetes, wound healing, fibrosis and infectious diseases and either improve or worsen the course of diseases depending on the matricryptins and on the molecular and biological contexts. Several protease families release matricryptins from core-matrisome and matrisome-associated proteins both in vitro and in vivo. The major proteases, which decrypt the extracellular matrix, are zinc metalloproteinases of the metzincin superfamily (matrixins, adamalysins and astacins), cysteine proteinases and serine proteases. Some matricryptins act as enzyme inhibitors, further connecting protease and matricryptin fates and providing intricate regulation of major physiopathological processes such as angiogenesis and tumorigenesis. They strengthen the role of the extracellular matrix as a key player in tissue failure and core-matrisome and matrisome-associated proteins as important therapeutic targets.
authors.affiliation: UMR 5086 CNRS - Université Lyon 1, 7 Passage du Vercors, 69367 Lyon Cedex 07, France. Electronic address: s.ricard-blum@ibcp.fr.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Ricard-Blum
authors.affiliation: UMR 5086 CNRS - Université Lyon 1, 7 Passage du Vercors, 69367 Lyon Cedex 07, France. Electronic address: sylvain-daniel.vallet@ibcp.fr.
authors.forename: Sylvain D
authors.initials: SD
authors.lastname: Vallet
mesh_terms: D000818:Animals; D005109:Extracellular Matrix / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D006025:Glycosaminoglycans / Q000378:metabolism*; D006801:Humans; D008666:Metalloendopeptidases / Q000378:metabolism*; D008954:Models, Biological; D010829:Physiological Phenomena; D059748:Proteolysis; D040901:Proteomics
chemical_list: D016326:Extracellular Matrix Proteins; D006025:Glycosaminoglycans; D008666:Metalloendopeptidases
keywords: Bioactive fragments; Cryptome; Extracellular matrix; Matricryptins; Proteases