Fragments generated upon extracellular matrix remodeling: Biological regulators and potential drugs

The remodeling of the extracellular matrix (ECM) by several protease families releases a number of bioactive fragments, which regulate numerous biological processes such as autophagy, angiogenesis, adipogenesis, fibrosis, tumor growth, metastasis and wound healing. We review here the proteases which...

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Bibliographic Details
Published in:Matrix biology 2019-01, Vol.75-76, p.170-189
Main Authors: Ricard-Blum, Sylvie, Vallet, Sylvain D.
Format: Article
Language:English
Subjects:
Adipogenesis
Angiogenesis
Autophagy
Biochemistry
Biochemistry, Molecular Biology
Drugs
Extracellular matrix
Fibrosis
Life Sciences
Mathematical models
Matrikines
Metastases
Phagocytosis
Proteases
Receptor mechanisms
Receptors
Remodeling
Wound healing
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Summary:The remodeling of the extracellular matrix (ECM) by several protease families releases a number of bioactive fragments, which regulate numerous biological processes such as autophagy, angiogenesis, adipogenesis, fibrosis, tumor growth, metastasis and wound healing. We review here the proteases which generate bioactive ECM fragments, their ECM substrates, the major bioactive ECM fragments, together with their biological properties and their receptors. The translation of ECM fragments into drugs is challenging and would take advantage of an integrative approach to optimize the design of pre-clinical and clinical studies. This could be done by building the contextualized interaction network of the ECM fragment repertoire including their parent proteins, remodeling proteinases, and their receptors, and by using mathematical disease models. •Zinc, serine or cysteine proteases release ECM bioactive fragments during ECM remodeling.•Bioactive ECM fragments regulate major biological processes (e.g. angiogenesis, tumor growth, fibrosis, and adipogenesis).•Different ECM fragments may regulate the same biological process.•ECM fragments modulate gene expression, cell signaling and enzyme activation/activity.•ECM fragments are potential drugs and are diagnostic and prognostic markers of diseases.
ISSN:0945-053X
1569-1802
DOI:10.1016/j.matbio.2017.11.005