The extracellular matrix as a multitasking player in disease

Abstract

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.

Profile of Matrix-Remodeling Proteinases in Osteoarthritis: Impact of Fibronectin

“…ECM is involved in many cell functions, providing cells with chemical and mechanical signals to regulate cell proliferation, survival, migration, and differentiation. However, changes in the composition and physical properties of the ECM lead to the development of many diseases, including cancer and rheumatic diseases, such as OA and rheumatoid arthritis (RA), among others [5,6]. Moreover, cell stress and ECM degradation promote maladaptive healing reactions, including inflammatory pathways of innate and adaptive immunity [7].…”

“…Among the fibrillary components of ECM, the glycoprotein fibronectin (Fn) is an important member that acts as a bridging molecule in matrix assembly and cell-matrix interfaces. During the development of OA, tissue proteolysis and injury induce ECM degradation generating Fn fragments (Fn-fs), among other catabolic mediators, that promote inflammation and degradation by the induction of cytokine [8] and proteinase expressions [5]. This review focuses on the emerging issues related to the role of Fn-fs in the inflammatory cascade through the stimulation of urokinase-type plasminogen activator (uPA), matrix metalloproteinases (MMPs), and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTSs) proteinases in OA.…”

Cell motion-coordinated fibrillar assembly of soluble collagen I to promote MDCK cell branching formation

“…COL fiber assembly/remodeling is highly regulated by biomechanical and biochemical processes [17,26,27]. ECM assembly and remodeling driven by cells represent more physiological processes occurring in vivo [9]. Our work revealed that cell mobility was an active factor in facilitating cells-mediated COL fibrillar assembly from the medium.…”

“…ECM assembly and remodeling are critical physiological events in vivo, and abnormal ECM assembly or remodeling is involved into pathological conditions such as osteoarthritis, fibrosis, cancers, and genetic diseases [9]. ECM assembly is mediated by both biochemical processes and mechanical force, and force on ECM regulates ECM remodeling, ligand binding, and homeostasis [10].…”

Loss of the extracellular matrix molecule tenascin-C leads to absence of reactive gliosis and promotes anti-inflammatory cytokine expression in an autoimmune glaucoma mouse model

“…cellular key events such as adhesion, differentiation, migration, proliferation as well as survival 43 (Hynes, 2009;Theocharidis et al, 2014;Faissner and Reinhard, 2015;Krishnaswamy et al, 2019;44 Roll and Faissner, 2019; Theocharis et al, 2019). ECM molecules can provide an inhibitory 45 environment for neural regeneration and migration in the retina (Reinhard et al, 2015).…”