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

Abstract

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.

A novel protocol for the isolation of fungal extracellular vesicles reveals the participation of a putative scramblase in polysaccharide export and capsule construction in Cryptococcus gattii.

“…In this environment, they participate in matrix organization, regulation of cellular functions and determination of the physical properties of different tissues (19). EVs produced in gelatinous matrices impact tissue regeneration, inflammation and tumor progression (18, 19). With a few exceptions (e.g.…”

Induced Pluripotent Stem Cells Attenuate Endothelial Leakage in Acute Lung Injury via Tissue Inhibitor of Metalloproteinases-1 to Reduce Focal Adhesion Kinase Activity

“…In this study, we did not directly check how TIMP-1 was secreted into iPSC-CM. Previous study [41] has identified several extracellular vesicleswww.StemCells.com ©AlphaMed Press 2019…”

“…In this study, we did not directly check how TIMP‐1 was secreted into iPSC‐CM. Previous study has identified several extracellular vesicles‐associated MMPs and TIMPs in various types of cells. Recent study suggest that MSC‐derived extracellular vesicles might carry immunomodulatory factors of MSCs, which could be used as the treatment of inflammatory diseases via direct immunosuppressive function.…”

Are the Matrix Metalloproteinases 2 and 9 beeing expressed in the mucosa of the rat small intestine during its intrauterine and postnatal life development ?

“…It is known that MMP-2 and MMP-9 are involved in the remodeling and signalization process of the extracellular matrix such as the modulation of the biological growth factors and cell proliferation in normal tissue developmental repair or during the progression of several degenerative diseases (Stamenkovic 2003, Phillips et al, 2017, Nawaz et al, 2018). To perform these functions MMPs are actively expressed by different types of cells like keratinocytes, endothelial cells, fibroblasts, chondroblasts, immune system and Schwann cells (Chattopadhyay and Shubayev 2009, Zambuzzi et al 2009, Vaillant et al 2003).…”