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Extracellular Vesicles and Matrix Remodeling Enzymes: The Emerging Roles in Extracellular Matrix Remodeling, Progression of Diseases and Tissue Repair

Journal article
Authors Muhammad Nawaz
N. Shah
B. R. Zanetti
Maugeri Marco
R. N. Silvestre
F. Fatima
L. Neder
Hadi Valadi
Published in Cells
Volume 7
Issue 10
ISSN 2073-4409
Publication year 2018
Published at Institute of Medicine, Department of Rheumatology and Inflammation Research
Language en
Keywords extracellular vesicles, exosomes, matrix metalloproteinases, MMPs, extracellular matrix, telocytes, epithelial-mesenchymal transition, cells stimulate angiogenesis, growth-factor beta-1, membrane-vesicles, stem-cells, endothelial-cells, ovarian-cancer, in-vitro, horizontal transfer, cardiovascular-disease, Cell Biology
Subject categories Clinical Medicine


Extracellular vesicles (EVs) are membrane enclosed micro- and nano-sized vesicles that are secreted from almost every species, ranging from prokaryotes to eukaryotes, and from almost every cell type studied so far. EVs contain repertoire of bioactive molecules such as proteins (including enzymes and transcriptional factors), lipids, carbohydrates and nucleic acids including DNA, coding and non-coding RNAs. The secreted EVs are taken up by neighboring cells where they release their content in recipient cells, or can sail through body fluids to reach distant organs. Since EVs transport bioactive cargo between cells, they have emerged as novel mediators of extra- and intercellular activities in local microenvironment and inter-organ communications distantly. Herein, we review the activities of EV-associated matrix-remodeling enzymes such as matrix metalloproteinases, heparanases, hyaluronidases, aggrecanases, and their regulators such as extracellular matrix metalloproteinase inducers and tissue inhibitors of metalloproteinases as novel means of matrix remodeling in physiological and pathological conditions. We discuss how such EVs act as novel mediators of extracellular matrix degradation to prepare a permissive environment for various pathological conditions such as cancer, cardiovascular diseases, arthritis and metabolic diseases. Additionally, the roles of EV-mediated matrix remodeling in tissue repair and their potential applications as organ therapies have been reviewed. Collectively, this knowledge could benefit the development of new approaches for tissue engineering.

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