title: Extracellular matrix remodeling: the common denominator in connective tissue diseases. Possibilities for evaluation and current understanding of the matrix as more than a passive architecture, but a key player in tissue failure.
abstract: Increased attention is paid to the structural components of tissues. These components are mostly collagens and various proteoglycans. Emerging evidence suggests that altered components and noncoded modifications of the matrix may be both initiators and drivers of disease, exemplified by excessive tissue remodeling leading to tissue stiffness, as well as by changes in the signaling potential of both intact matrix and fragments thereof. Although tissue structure until recently was viewed as a simple architecture anchoring cells and proteins, this complex grid may contain essential information enabling the maintenance of the structure and normal functioning of tissue. The aims of this review are to (1) discuss the structural components of the matrix and the relevance of their mutations to the pathology of diseases such as fibrosis and cancer, (2) introduce the possibility that post-translational modifications (PTMs), such as protease cleavage, citrullination, cross-linking, nitrosylation, glycosylation, and isomerization, generated during pathology, may be unique, disease-specific biochemical markers, (3) list and review the range of simple enzyme-linked immunosorbent assays (ELISAs) that have been developed for assessing the extracellular matrix (ECM) and detecting abnormal ECM remodeling, and (4) discuss whether some PTMs are the cause or consequence of disease. New evidence clearly suggests that the ECM at some point in the pathogenesis becomes a driver of disease. These pathological modified ECM proteins may allow insights into complicated pathologies in which the end stage is excessive tissue remodeling, and provide unique and more pathology-specific biochemical markers.
authors.affiliation: Nordic Bioscience A/S, Herlev Hovedgade, Herlev, Denmark. mk@nordicbioscience.com
authors.forename: Morten A
authors.initials: MA
authors.lastname: Karsdal
authors.forename: Mette J
authors.initials: MJ
authors.lastname: Nielsen
authors.forename: Jannie M
authors.initials: JM
authors.lastname: Sand
authors.forename: Kim
authors.initials: K
authors.lastname: Henriksen
authors.forename: Federica
authors.initials: F
authors.lastname: Genovese
authors.forename: Anne-Christine
authors.initials: AC
authors.lastname: Bay-Jensen
authors.forename: Victoria
authors.initials: V
authors.lastname: Smith
authors.forename: Joanne I
authors.initials: JI
authors.lastname: Adamkewicz
authors.forename: Claus
authors.initials: C
authors.lastname: Christiansen
authors.forename: Diana J
authors.initials: DJ
authors.lastname: Leeming
mesh_terms: D000818:Animals; D003240:Connective Tissue Diseases / Q000378:metabolism* / Q000473:pathology; D055119:Elastic Modulus; D005109:Extracellular Matrix / Q000378:metabolism* / Q000473:pathology; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D011499:Protein Processing, Post-Translational
chemical_list: D016326:Extracellular Matrix Proteins