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Advanced Research on Matrix Metalloproteinases (MMPs)
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Advanced Research on Matrix Metalloproteinases (MMPs)

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 (10 February 2023) | Viewed by 15514

Special Issue Editor

Dr. Cristina Sánchez-Camacho

E-Mail Website
Guest Editor
Faculty of Biology, Department of Genetics, Physiology and Microbiology, Universidad Complutense de Madrid, 28040 Madrid, Spain
Interests: membrane-type metalloproteinases (MT-MMPs); MT1-MMP; MT4-MMP; embryonic development; neurodevelopment; angiogenesis

Special Issue Information

Dear Colleagues,

Matrix Metalloproteinases (MMPs) belong to the zinc-dependent superfamily of endopeptidases found in all cell organisms. They function as key regulators of many physiological and pathological processes through the degradation and remodeling of the extracellular matrix. Furthermore, they are able to activate a variety of molecules through proteolytic cleavage, such as growth factors, receptors, cytokines, and adhesion molecules. Over the last few decades, increasing numbers of studies have supported the essential role of MMPs during embryogenesis when important developmental processes that require the modification of the extracellular environment take place. However, the involvement of MMPs in distinct morphogenetic events, such as cell migration and proliferation, cell polarity, angiogenesis, axon guidance, and synapse formation, necessitate further studies in order to understand the underlying molecular mechanisms that occur in the embryo.

This Special Issue of the International Journal of Molecular Sciences focuses on the function of MMPs during embryonic development as well as their implications for diseases such cancer and neurodegenerative disorders. We welcome both original research articles and review papers that deal with the molecular mechanisms underlying the role of MMP signaling during embryogenesis and disease.

Dr. Cristina Sánchez-Camacho
Guest Editor

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

  • matrix metalloproteinases
  • embryonic development
  • cell polarity
  • synaptogenesis
  • axon growth and guidance
  • cell migration and proliferation
  • angiogenesis
  • lymphangiogenesis
  • branching morphogenesis

Published Papers (6 papers)

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Research

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13 pages, 2524 KiB  
Article
Characterization of Dense Granule Metalloproteinase INS-16 in Cryptosporidium parvum
by Hao Cui, Rui Xu, Yu Li, Yaqiong Guo, Ziding Zhang, Lihua Xiao, Yaoyu Feng and Na Li
Int. J. Mol. Sci. 2022, 23(14), 7617; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23147617 - 10 Jul 2022
Cited by 3 | Viewed by 1442
Abstract
The protozoan pathogen Cryptosporidium parvum infects intestinal epithelial cells and causes diarrhea in humans and young animals. Among the more than 20 genes encoding insulinase-like metalloproteinases (INS), two are paralogs with high sequence identity. In this study, one of them, INS-16 encoded by [...] Read more.
The protozoan pathogen Cryptosporidium parvum infects intestinal epithelial cells and causes diarrhea in humans and young animals. Among the more than 20 genes encoding insulinase-like metalloproteinases (INS), two are paralogs with high sequence identity. In this study, one of them, INS-16 encoded by the cgd3_4270 gene, was expressed and characterized in a comparative study of its sibling, INS-15 encoded by the cgd3_4260 gene. A full-length INS-16 protein and its active domain I were expressed in Escherichia coli, and antibodies against the domain I and an INS-16-specific peptide were produced in rabbits. In the analysis of the crude extract of oocysts, a ~60 kDa fragment of INS-16 rather than the full protein was recognized by polyclonal antibodies against the specific peptide, indicating that INS-16 undergoes proteolytic cleavage before maturation. The expression of the ins-16 gene peaked at the invasion phase of in vitro C. parvum culture, with the documented expression of the protein in both sporozoites and merozoites. Localization studies with antibodies showed significant differences in the distribution of the native INS-15 and INS-16 proteins in sporozoites and merozoites. INS-16 was identified as a dense granule protein in sporozoites and macrogamonts but was mostly expressed at the apical end of merozoites. We screened 48 candidate INS-16 inhibitors from the molecular docking of INS-16. Among them, two inhibited the growth of C. parvum in vitro (EC50 = 1.058 µM and 2.089 µM). The results of this study suggest that INS-16 may have important roles in the development of C. parvum and could be a valid target for the development of effective treatments. Full article
(This article belongs to the Special Issue Advanced Research on Matrix Metalloproteinases (MMPs))
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Review

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14 pages, 3003 KiB  
Review
Molecular Mechanisms Driven by MT4-MMP in Cancer Progression
by Emma Muñoz-Sáez, Natalia Moracho, Ana I. R. Learte, Alice Collignon, Alicia G. Arroyo, Agnés Noel, Nor Eddine Sounni and Cristina Sánchez-Camacho
Int. J. Mol. Sci. 2023, 24(12), 9944; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24129944 - 09 Jun 2023
Cited by 2 | Viewed by 1229
Abstract
MT4-MMP (or MMP-17) belongs to the membrane-type matrix metalloproteinases (MT-MMPs), a distinct subset of the MMP family that is anchored to the cell surface, in this case by a glycosylphosphatidylinositol (GPI) motif. Its expression in a variety of cancers is well documented. However, [...] Read more.
MT4-MMP (or MMP-17) belongs to the membrane-type matrix metalloproteinases (MT-MMPs), a distinct subset of the MMP family that is anchored to the cell surface, in this case by a glycosylphosphatidylinositol (GPI) motif. Its expression in a variety of cancers is well documented. However, the molecular mechanisms by which MT4-MMP contributes to tumor development need further investigation. In this review, we aim to summarize the contribution of MT4-MMP in tumorigenesis, focusing on the molecular mechanisms triggered by the enzyme in tumor cell migration, invasiveness, and proliferation, in the tumor vasculature and microenvironment, as well as during metastasis. In particular, we highlight the putative substrates processed and signaling cascades activated by MT4-MMP that may underlie these malignancy processes and compare this with what is known about its role during embryonic development. Finally, MT4-MMP is a relevant biomarker of malignancy that can be used for monitoring cancer progression in patients as well as a potential target for future therapeutic drug development. Full article
(This article belongs to the Special Issue Advanced Research on Matrix Metalloproteinases (MMPs))
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16 pages, 2886 KiB  
Review
Comprehensive Analysis of the Prognostic Value of Circulating MMP-7 Levels in Urothelial Carcinoma: A Combined Cohort Analysis, Systematic Review, and Meta-Analysis
by András Kubik, Isabel Pinto Amorim das Virgens, Anett Szabó, Melinda Váradi, Anita Csizmarik, Attila Keszthelyi, Attila Majoros, Péter Fehérvári, Péter Hegyi, Nándor Ács, Péter Nyirády and Tibor Szarvas
Int. J. Mol. Sci. 2023, 24(9), 7859; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24097859 - 26 Apr 2023
Cited by 2 | Viewed by 1641
Abstract
Lymph node (LN) status is the most significant prognostic factor for invasive urothelial bladder cancer (UBC); however, the optimal extent of LN dissection (LND) is debated. We assessed circulating matrix metalloproteinase-7 (MMP-7) as a prognostic factor and decision-making marker for the extent of [...] Read more.
Lymph node (LN) status is the most significant prognostic factor for invasive urothelial bladder cancer (UBC); however, the optimal extent of LN dissection (LND) is debated. We assessed circulating matrix metalloproteinase-7 (MMP-7) as a prognostic factor and decision-making marker for the extent of LND. Preoperative serum MMP-7 levels were determined in two independent UBC cohorts (n = 188; n = 68) and in one control cohort (n = 97) by using the ELISA method. A systematic review and meta-analysis on the prognostic role of circulating pretreatment MMP-7 levels were performed. Serum MMP-7 levels were higher in patients compared to controls (p < 0.001) with the highest levels in LN-positive cases. Half of LN-positive UBC patients had low MMP-7 levels, whereas the survival of LN-negative patients with high serum MMP-7 findings was poor. MMP-7 levels were independently associated with poor survival in both cohorts (p = 0.006, p < 0.001). Accordingly, our systematic review of six eligible publications revealed a 2.5-fold higher mortality risk in patients with high MMP-7 levels. In conclusion, preoperative MMP-7 level is a validated and independent prognostic factor in urothelial cancer. It cannot be used to decide between regional or extended LND but may be useful in identifying LN-negative high-risk patients with potentially undetected metastases. Full article
(This article belongs to the Special Issue Advanced Research on Matrix Metalloproteinases (MMPs))
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20 pages, 3323 KiB  
Review
Matrix Metalloproteinases in Chronic Obstructive Pulmonary Disease
by Maria-Elpida Christopoulou, Eleni Papakonstantinou and Daiana Stolz
Int. J. Mol. Sci. 2023, 24(4), 3786; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24043786 - 14 Feb 2023
Cited by 13 | Viewed by 2636
Abstract
Matrix metalloproteinases (MMPs) are proteolytic enzymes that degrade proteins of the extracellular matrix and the basement membrane. Thus, these enzymes regulate airway remodeling, which is a major pathological feature of chronic obstructive pulmonary disease (COPD). Furthermore, proteolytic destruction in the lungs may lead [...] Read more.
Matrix metalloproteinases (MMPs) are proteolytic enzymes that degrade proteins of the extracellular matrix and the basement membrane. Thus, these enzymes regulate airway remodeling, which is a major pathological feature of chronic obstructive pulmonary disease (COPD). Furthermore, proteolytic destruction in the lungs may lead to loss of elastin and the development of emphysema, which is associated with poor lung function in COPD patients. In this literature review, we describe and appraise evidence from the recent literature regarding the role of different MMPs in COPD, as well as how their activity is regulated by specific tissue inhibitors. Considering the importance of MMPs in COPD pathogenesis, we also discuss MMPs as potential targets for therapeutic intervention in COPD and present evidence from recent clinical trials in this regard. Full article
(This article belongs to the Special Issue Advanced Research on Matrix Metalloproteinases (MMPs))
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12 pages, 991 KiB  
Review
Association of MMP-2 and MMP-9 Polymorphisms with Diabetes and Pathogenesis of Diabetic Complications
by Beata Gajewska and Mariola Śliwińska-Mossoń
Int. J. Mol. Sci. 2022, 23(18), 10571; https://doi.org/10.3390/ijms231810571 - 12 Sep 2022
Cited by 6 | Viewed by 3763
Abstract
Type 2 diabetes mellitus (T2D) affects millions of people around the world, and its complications have serious health consequences. In addition to external factors, the causes of morbidity and increased risk were also sought in the variability of the human genome. A phenomenon [...] Read more.
Type 2 diabetes mellitus (T2D) affects millions of people around the world, and its complications have serious health consequences. In addition to external factors, the causes of morbidity and increased risk were also sought in the variability of the human genome. A phenomenon that can answer these questions is the occurrence of single-nucleotide polymorphisms (SNP). They constitute a field for research into genetic determinants responsible for the increase in the risk of the discussed metabolic disease. This article presents the outline of two enzymes: metalloproteinases 2 and 9 (MMP-2, MMP-9), their biological activity and the effect caused by differences in individual alleles in the population, as well as the reports on the importance of these DNA sequence variations in the occurrence of diabetes mellitus type 2 and associated conditions. The results of the conducted research indicate a relationship between two MMP-2 polymorphisms (rs243865, rs243866) and two MMP-9 polymorphisms (rs3918242, rs17576) and the presence of T2D. This could offer a promising possibility to use them as predictive and diagnostic markers. However, due to the low number of reports, more research is needed to clearly confirm the link between these SNPs and diabetes. Full article
(This article belongs to the Special Issue Advanced Research on Matrix Metalloproteinases (MMPs))
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18 pages, 388 KiB  
Review
The Role of Matrix Metalloproteinase in Inflammation with a Focus on Infectious Diseases
by Han Sol Lee and Woo Joo Kim
Int. J. Mol. Sci. 2022, 23(18), 10546; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms231810546 - 11 Sep 2022
Cited by 22 | Viewed by 3886
Abstract
Matrix metalloproteinases (MMPs) are involved in extracellular matrix remodeling through the degradation of extracellular matrix components and are also involved in the inflammatory response by regulating the pro-inflammatory cytokines TNF-α and IL-1β. Dysregulation in the inflammatory response and changes in the extracellular matrix [...] Read more.
Matrix metalloproteinases (MMPs) are involved in extracellular matrix remodeling through the degradation of extracellular matrix components and are also involved in the inflammatory response by regulating the pro-inflammatory cytokines TNF-α and IL-1β. Dysregulation in the inflammatory response and changes in the extracellular matrix by MMPs are related to the development of various diseases including lung and cardiovascular diseases. Therefore, numerous studies have been conducted to understand the role of MMPs in disease pathogenesis. MMPs are involved in the pathogenesis of infectious diseases through a dysregulation of the activity and expression of MMPs. In this review, we discuss the role of MMPs in infectious diseases and inflammatory responses. Furthermore, we present the potential of MMPs as therapeutic targets in infectious diseases. Full article
(This article belongs to the Special Issue Advanced Research on Matrix Metalloproteinases (MMPs))
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