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

作者：M.A. Karsdal, Mette Juul Nielsen, Jannie Marie Bülow Sand, Kim Henriksen, Federica Genovese, Anne‐Christine Bay‐Jensen, Victoria Smith, Joanne I. Adamkewicz, Claus Christiansen, Diana Julie Leeming · 发表于：Assay and Drug Development Technologies · 年份：2012 · DOI：10.1089/adt.2012.474 · 被引用次数：286 · 研究领域：Protease and Inhibitor Mechanisms、Connective Tissue Growth Factor Research、Connective tissue disorders research

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 path...