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The extracellular matrix as a multitasking player in disease.

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  • The extracellular matrix as a multitasking player in disease. FULL TEXT AVAILABLE.
    The extracellular matrix as a multitasking player in disease.
    Extracellular matrices (ECMs) are highly specialized and dynamic three-dimensional (3D) scaffolds into which cells reside in tissues. ECM is composed of a variety of fibrillar components, such as collagens, fibronectin, and elastin, and non-fibrillar molecules as proteoglycans, hyaluronan, and glycoproteins including matricellular proteins. These macromolecular components are interconnected forming complex networks that actively communicate with cells through binding to cell surface receptors and/or matrix effectors. ECMs exert diverse roles, either providing tissues with structural integrity and mechanical properties essential for tissue functions or regulating cell phenotype and functions to maintain tissue homeostasis. ECM molecular composition and structure vary among tissues, and is markedly modified during normal tissue repair as well as during the progression of various diseases. Actually, abnormal ECM remodeling occurring in pathologic circumstances drives disease progression by regulating cell-matrix interactions. The importance of matrix molecules to normal tissue functions is also highlighted by mutations in matrix genes that give rise to genetic disorders with diverse clinical phenotypes. In this review, we present critical and emerging issues related to matrix assembly in tissues and the multitasking roles for ECM in diseases such as osteoarthritis, fibrosis, cancer, and genetic diseases. The mechanisms underlying the various matrix-based diseases are also discussed. Research focused on the highly dynamic 3D ECM networks will help to discover matrix-related causative abnormalities of diseases as well as novel diagnostic tools and therapeutic targets.

    © 2019 Federation of European Biochemical Societies
    Concluding remarks and perspectives
    Extracellular matrix is a key regulator of tissue organization and homeostasis. ECM provides chemical and mechanical signals to cells regulating their phenotype and responses to coordinate tissue functions. Matrix molecules are interconnected by interacting with each other creating a functional meshwork that also dynamically interacts with cell surface receptors on resident cells. Cell–matrix interactions are essential for proper cell and tissue functionality. The development and progression of various diseases including fibrosis, cancer, and osteoarthritis are associated with abnormal ECM remodeling. In addition, mutations of matrix‐associated genes also markedly affect tissue organization and functions and lead to the development of genetic disorders with variable clinical phenotypes. The last years a plethora of ECM molecules have been emerged as valuable targets for disease prognosis and treatment. Hence, it is of great importance to unravel the molecular mechanisms underlying abnormal ECM remodeling and their involvement in diseases. The deeper understanding of the molecular interactions between matrix molecules as well as the modified cell–matrix interactions and their effect on cell signaling are fundamental. This will help us to design novel ECM‐based strategies for disease treatment.