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The MMPs and Its Associated Proteins and Substrates on the Cell

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: closed (31 May 2023) | Viewed by 9341

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Special Issue Editors

Dr. Kyu-Yeon Han

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Guest Editor

Department of Ophthalmology and Visual Sciences, Illinois Eye and Ear Infirmary, College of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA
Interests: matrix metalloproteinases; VEGF and VEGF receptors; MMPs inhibitors; angiogenesis; wound healing; cornea
Special Issues, Collections and Topics in MDPI journals

Dr. Hyun Lee

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Guest Editor

Department of Pharmaceutical Sciences, College of Pharmacy, University of Illinois at Chicago, Chicago, IL 60612, USA
Interests: drug discovery and development; small molecule inhibitors; protein–protein interaction; MMPs inhibitors, MERS-CoV; SARS-CoV-1 and -2; infectious diseases; high-throughput screening; enzymatic assays

Special Issue Information

Dear Colleagues,

Matrix metalloproteinases (MMPs) belong to a superfamily of metzincins that contain a zinc-binding domain. MMPs are known to be important enzymes in modifying the extracellular environment during various biological processes, such as wound healing, angiogenesis, and cancer metastasis.

New roles of MMP have been identified whenever novel MMP substrates are revealed. Here, we would like to summarize the substrates of MMP that have been identified so far and the roles of MMP accordingly.

This Special Issue aims to provide an up-to-date overview of MMP substrates and the expanding functions of MMPs.

Dr. Kyu-Yeon Han
Dr. Hyun Lee
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

MT1-MMP
protein tyrosine kinases
VEGFRs
angiogenesis
MMPs inhibitors
corneal diseases

Published Papers (5 papers)

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Research

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13 pages, 13489 KiB

Open AccessArticle

The Reparative Function of MMP13 in Tertiary Reactionary Dentinogenesis after Tooth Injury

by Henry F. Duncan, Yoshifumi Kobayashi, Yukako Yamauchi and Emi Shimizu

Int. J. Mol. Sci. 2024, 25(2), 875; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms25020875 - 10 Jan 2024

Viewed by 623

Abstract

MMP13 gene expression increases up to 2000-fold in mineralizing dental pulp cells (DPCs), with research previously demonstrating that global MMP13 deletion resulted in critical alterations in the dentine phenotype, affecting dentine–tubule regularity, the odontoblast palisade, and significantly reducing the dentine volume. Global MMP13-KO and wild-type mice of a range of ages had their molar teeth injured to stimulate reactionary tertiary dentinogenesis. The response was measured qualitatively and quantitatively using histology, immunohistochemistry, micro-CT, and qRT-PCR in order to assess changes in the nature and volume of dentine deposited as well as mechanistic links. MMP13 loss affected the reactionary tertiary dentine quality and volume after cuspal injury and reduced Nestin expression in a non-exposure injury model, as well as mechanistic links between MMP13 and the Wnt-responsive gene Axin2. Acute pulpal injury and pulp exposure to oral fluids in mice teeth showed upregulation of the MMP13 in vivo, with an increase in the gene expression of Mmp8, Mmp9, and Mmp13 evident. These results indicate that MMP13 is involved in tertiary reactionary dentine formation after tooth injury in vivo, potentially acting as a key molecule in the dental pulp during dentine–pulp repair processes. Full article

(This article belongs to the Special Issue The MMPs and Its Associated Proteins and Substrates on the Cell)

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Review

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27 pages, 1536 KiB

Open AccessReview

Hypoxic Effects on Matrix Metalloproteinases’ Expression in the Tumor Microenvironment and Therapeutic Perspectives

by Georgina Gonzalez-Avila, Bettina Sommer, Edgar Flores-Soto and Arnoldo Aquino-Galvez

Int. J. Mol. Sci. 2023, 24(23), 16887; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms242316887 - 28 Nov 2023

Cited by 1 | Viewed by 1084

Abstract

The tumor microenvironment (TME) is characterized by an acidic pH and low oxygen concentrations. Hypoxia induces neoplastic cell evasion of the immune surveillance, rapid DNA repair, metabolic reprogramming, and metastasis, mainly as a response to the hypoxic inducible factors (HIFs). Likewise, cancer cells increase matrix metalloproteinases’ (MMPs) expression in response to TME conditions, allowing them to migrate from the primary tumor to different tissues. Since HIFs and MMPs are augmented in the hypoxic TME, it is easy to consider that HIFs participate directly in their expression regulation. However, not all MMPs have a hypoxia response element (HRE)-HIF binding site. Moreover, different transcription factors and signaling pathways activated in hypoxia conditions through HIFs or in a HIF-independent manner participate in MMPs’ transcription. The present review focuses on MMPs’ expression in normal and hypoxic conditions, considering HIFs and a HIF-independent transcription control. In addition, since the hypoxic TME causes resistance to anticancer conventional therapy, treatment approaches using MMPs as a target alone, or in combination with other therapies, are also discussed. Full article

(This article belongs to the Special Issue The MMPs and Its Associated Proteins and Substrates on the Cell)

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20 pages, 3270 KiB

Open AccessReview

Cytoplasmic Tail of MT1-MMP: A Hub of MT1-MMP Regulation and Function

by Katerina Strouhalova, Ondřej Tolde, Daniel Rosel and Jan Brábek

Int. J. Mol. Sci. 2023, 24(6), 5068; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24065068 - 07 Mar 2023

Cited by 3 | Viewed by 1667

Abstract

MT1-MMP (MMP-14) is a multifunctional protease that regulates ECM degradation, activation of other proteases, and a variety of cellular processes, including migration and viability in physiological and pathological contexts. Both the localization and signal transduction capabilities of MT1-MMP are dependent on its cytoplasmic domain that constitutes the final 20 C-terminal amino acids, while the rest of the protease is extracellular. In this review, we summarize the ways in which the cytoplasmic tail is involved in regulating and enacting the functions of MT1-MMP. We also provide an overview of known interactors of the MT1-MMP cytoplasmic tail and the functional significance of these interactions, as well as further insight into the mechanisms of cellular adhesion and invasion that are regulated by the cytoplasmic tail. Full article

(This article belongs to the Special Issue The MMPs and Its Associated Proteins and Substrates on the Cell)

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16 pages, 3437 KiB

Open AccessReview

The Role of Membrane-Type 1 Matrix Metalloproteinase–Substrate Interactions in Pathogenesis

by Hyun Lee, Lucas Ibrahimi, Dimitri T. Azar and Kyu-Yeon Han

Int. J. Mol. Sci. 2023, 24(3), 2183; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24032183 - 22 Jan 2023

Cited by 2 | Viewed by 1702

Abstract

A protease is an enzyme with a proteolytic activity that facilitates the digestion of its substrates. Membrane-type I matrix metalloproteinase (MT1-MMP), a member of the broader matrix metalloproteinases (MMP) family, is involved in the regulation of diverse cellular activities. MT1-MMP is a very well-known enzyme as an activator of pro-MMP-2 and two collagenases, MMP-8 and MMP-13, all of which are essential for cell migration. As an anchored membrane enzyme, MT1-MMP has the ability to interact with a diverse group of molecules, including proteins that are not part of the extracellular matrix (ECM). Therefore, MT1-MMP can regulate various cellular activities not only by changing the extra-cellular environment but also by regulating cell signaling. The presence of both intracellular and extra-cellular portions of MT1-MMP can allow it to interact with proteins on both sides of the cell membrane. Here, we reviewed the MT1-MMP substrates involved in disease pathogenesis. Full article

(This article belongs to the Special Issue The MMPs and Its Associated Proteins and Substrates on the Cell)

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17 pages, 1558 KiB

Open AccessReview

Novel Roles of MT1-MMP and MMP-2: Beyond the Extracellular Milieu

by Deanna V. Maybee, Nicole L. Ink and Mohammad A. M. Ali

Int. J. Mol. Sci. 2022, 23(17), 9513; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23179513 - 23 Aug 2022

Cited by 17 | Viewed by 3391

Abstract

Matrix metalloproteinases (MMPs) are critical enzymes involved in a variety of cellular processes. MMPs are well known for their ability to degrade the extracellular matrix (ECM) and their extracellular role in cell migration. Recently, more research has been conducted on investigating novel subcellular localizations of MMPs and their intracellular roles at their respective locations. In this review article, we focus on the subcellular localization and novel intracellular roles of two closely related MMPs: membrane-type-1 matrix metalloproteinase (MT1-MMP) and matrix metalloproteinase-2 (MMP-2). Although MT1-MMP is commonly known to localize on the cell surface, the protease also localizes to the cytoplasm, caveolae, Golgi, cytoskeleton, centrosome, and nucleus. At these subcellular locations, MT1-MMP functions in cell migration, macrophage metabolism, invadopodia development, spindle formation and gene expression, respectively. Similar to MT1-MMP, MMP-2 localizes to the caveolae, mitochondria, cytoskeleton, nucleus and nucleolus and functions in calcium regulation, contractile dysfunction, gene expression and ribosomal RNA transcription. Our particular interest lies in the roles MMP-2 and MT1-MMP serve within the nucleus, as they may provide critical insights into cancer epigenetics and tumor migration and invasion. We suggest that targeting nuclear MT1-MMP or MMP-2 to reduce or halt cell proliferation and migration may lead to the development of new therapies for cancer and other diseases. Full article

(This article belongs to the Special Issue The MMPs and Its Associated Proteins and Substrates on the Cell)

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