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Biomolecules
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Role of Matrix Metalloproteinase in Health and Disease
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Role of Matrix Metalloproteinase in Health and Disease

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Molecular Medicine".

Deadline for manuscript submissions: closed (15 May 2025) | Viewed by 3109

Special Issue Editor

Dr. Ali A. Hussain

E-Mail Website
Guest Editor
UCL Institute of Ophthalmology, London, UK
Interests: macular degeneration; retinal electrophysiology; psychophysics; extracellular matrices; laser-tissue interactions

Special Issue Information

Dear Colleagues,

Matrix metalloproteinases (MMPs) are a diverse group of secreted and membrane-anchored endopeptidases that play essential roles primarily in maintaining the structural and functional integrity of extracellular matrices, with secondary roles in modulating the action of growth factors, cell surface receptors, cytokines, and chemokines, and thereby affecting signalling pathways. Abnormalities in the regulation and activity of MMPs have been associated with the ageing process and involvement in diseases such as cancers, cardiovascular and peripheral vascular diseases, inflammation, and neurodegenerative diseases such as age-related macular degeneration and Alzheimer’s.

Recent advances in the regulatory aspects of MMP activation, the compartmentalization between bound and free forms, and the post-translation modifications of both the enzyme and their substrates shed light on the underlying mechanisms operational in pathological circumstances, leading to their nomination as likely targets for therapeutic interventions.

This Special Issue of Biomolecules focuses on the role of MMPs in the aetiology and progression of pathological processes and the potential for therapeutic intervention targeting these enzymes. Original manuscripts and review articles addressing the role of MMPs in normal and pathological processes are most welcome.

Dr. Ali A. Hussain
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. Biomolecules is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). 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 (MMPs)
  • regulatory aspects of MMPs
  • MMPs and tissue ageing
  • MMPs in diseases
  • MMPs as therapeutic targets

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Published Papers (3 papers)

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Research

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28 pages, 8683 KiB  
Article
Suppression of MT5-MMP Reveals Early Modulation of Alzheimer’s Pathogenic Events in Primary Neuronal Cultures of 5xFAD Mice
by Dominika Pilat, Jean-Michel Paumier, Laurence Louis, Christine Manrique, Laura García-González, Delphine Stephan, Anne Bernard, Raphaëlle Pardossi-Piquard, Frédéric Checler, Michel Khrestchatisky, Eric Di Pasquale, Kévin Baranger and Santiago Rivera
Biomolecules 2024, 14(12), 1645; https://doi.org/10.3390/biom14121645 - 21 Dec 2024
Viewed by 1044
Abstract
We previously reported that membrane-type 5-matrix metalloproteinase (MT5-MMP) deficiency not only reduces pathological hallmarks of Alzheimer’s disease (AD) in 5xFAD (Tg) mice in vivo but also impairs interleukin-1 beta (IL-1β)-mediated neuroinflammation and Aβ production in primary Tg immature neural cell cultures after 11 days [...] Read more.
We previously reported that membrane-type 5-matrix metalloproteinase (MT5-MMP) deficiency not only reduces pathological hallmarks of Alzheimer’s disease (AD) in 5xFAD (Tg) mice in vivo but also impairs interleukin-1 beta (IL-1β)-mediated neuroinflammation and Aβ production in primary Tg immature neural cell cultures after 11 days in vitro. We now investigate the effect of MT5-MMP on incipient pathogenic pathways that are activated in cortical primary cultures at 21–24 days in vitro (DIV), during which time neurons are organized into a functional mature network. Using wild-type (WT), MT5-MMP−/− (MT5−/−), 5xFAD (Tg), and 5xFADxMT5-MMP−/− (TgMT5−/−) mice, we generated primary neuronal cultures that were exposed to IL-1β and/or different proteolytic system inhibitors. We assessed neuroinflammation, APP metabolism, synaptic integrity, and electrophysiological properties using biochemical, imaging and whole-cell patch-clamp approaches. The absence of MT5-MMP impaired the IL-1β-mediated induction of inflammatory genes in TgMT5−/− cells compared to Tg cells. Furthermore, the reduced density of dendritic spines in Tg neurons was also prevented in TgMT5−/− neurons. IL-1β caused a strong decrease in the dendritic spine density of WT neurons, which was prevented in MT5−/− neurons. However, the latter exhibited fewer spines than the WT under untreated conditions. The spontaneous rhythmic firing frequency of the network was increased in MT5−/− neurons, but not in TgMT5−/− neurons, and IL-1β increased this parameter only in Tg neurons. In terms of induced somatic excitability, Tg and TgMT5−/− neurons exhibited lower excitability than WT and MT5−/−, while IL-1β impaired excitability only in non-AD backgrounds. The synaptic strength of miniature global synaptic currents was equivalent in all genotypes but increased dramatically in WT and MT5−/− neurons after IL-1β. MT5-MMP deficiency decreased endogenous and overexpressed C83 and C99 levels but did not affect Aβ levels. C99 appears to be cleared by several pathways, including γ-secretase, the autophagolysosomal system, and also α-secretase, via its conversion to C83. In summary, this study confirms that MT5-MMP is a pivotal factor affecting not only neuroinflammation and APP metabolism but also synaptogenesis and synaptic activity at early stages of the pathology, and reinforces the relevance of targeting MT5-MMP to fight AD. Full article
(This article belongs to the Special Issue Role of Matrix Metalloproteinase in Health and Disease)
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10 pages, 899 KiB  
Article
The Influence of Bariatric Surgery on Matrix Metalloproteinase Plasma Levels in Patients with Type 2 Diabetes Mellitus
by João Kleber de Almeida Gentile, Renato Migliore, Jaques Waisberg and Marcelo Augusto Fontenelle Ribeiro Junior
Biomolecules 2024, 14(12), 1633; https://doi.org/10.3390/biom14121633 - 19 Dec 2024
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Abstract
Background: Bariatric surgery is a safe and effective procedure for treating obesity and metabolic conditions such as type 2 diabetes mellitus (T2DM). Remodeling of the extracellular matrix (ECM) supports adipose tissue expansion and its metabolic activity, where matrix metalloproteinases (MMPs) play a key [...] Read more.
Background: Bariatric surgery is a safe and effective procedure for treating obesity and metabolic conditions such as type 2 diabetes mellitus (T2DM). Remodeling of the extracellular matrix (ECM) supports adipose tissue expansion and its metabolic activity, where matrix metalloproteinases (MMPs) play a key role in ECM regulation. The MMPs, particularly MMP-2 and MMP-9, are elevated in patients with morbid obesity, metabolic syndrome, and T2DM. Objectives: To evaluate the effect of weight loss in bariatric surgery patients using oxidative stress markers and to compare MMP levels in patients undergoing bariatric surgery. Methods: This was a prospective, controlled study including 45 morbidly obese patients with T2DM (BMI > 35 kg/m2) who underwent RYGB (n = 24) or VG (n = 21). Weight loss was assessed through anthropometric measurements (weight, height, BMI). MMP-2 and MMP-9 levels were measured preoperatively and at 3 and 12 months postoperatively. Results: Significant and sustained weight loss was observed after surgery in both groups, with reductions in BMI. MMP-2 and MMP-9 levels decreased significantly after one year of follow-up. Conclusions: Bariatric surgery is an effective long-term intervention for weight loss and associated comorbidities, including T2DM. MMP-2 and MMP-9 proved to be effective markers of extracellular matrix remodeling, with significant reductions following surgery. Full article
(This article belongs to the Special Issue Role of Matrix Metalloproteinase in Health and Disease)
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Review

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23 pages, 1177 KiB  
Review
Matrix Metalloproteinases: Pathophysiologic Implications and Potential Therapeutic Targets in Cardiovascular Disease
by Daniela Maria Tanase, Emilia Valasciuc, Ioana-Bianca Anton, Evelina Maria Gosav, Nicoleta Dima, Andrei Ionut Cucu, Claudia Florida Costea, Diana Elena Floria, Loredana Liliana Hurjui, Claudia Cristina Tarniceriu, Manuela Ciocoiu and Mariana Floria
Biomolecules 2025, 15(4), 598; https://doi.org/10.3390/biom15040598 - 17 Apr 2025
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Abstract
Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases that play a crucial role in extracellular matrix (ECM) remodeling and are implicated in the pathogenesis of various cardiovascular diseases (CVDs). Their dysregulation has been linked to atherosclerosis, myocardial infarction (MI), heart failure (HF), [...] Read more.
Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases that play a crucial role in extracellular matrix (ECM) remodeling and are implicated in the pathogenesis of various cardiovascular diseases (CVDs). Their dysregulation has been linked to atherosclerosis, myocardial infarction (MI), heart failure (HF), and aortic stenosis, contributing to vascular inflammation, plaque destabilization, and adverse cardiac remodeling. Recent research highlights MMPs’ involvement beyond ECM degradation, influencing lipoprotein metabolism, inflammatory signaling, and intracellular processes critical for cardiovascular homeostasis. Despite their pathological role, MMPs remain promising therapeutic targets, with pharmacological inhibitors, gene therapy, and tissue inhibitors of metalloproteinases (TIMPs) emerging as potential interventions. However, the clinical translation of MMP-targeting therapies remains challenging due to off-target effects and complex regulatory mechanisms. This review provides an updated synthesis of the molecular mechanisms, disease-specific roles, and therapeutic implications of MMPs in cardiovascular pathology, aiming to bridge the gap between fundamental research and clinical applications. Full article
(This article belongs to the Special Issue Role of Matrix Metalloproteinase in Health and Disease)
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