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Role of microRNAs and Alarmins in Aging and Age-Related Diseases

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

Deadline for manuscript submissions: closed (31 March 2021) | Viewed by 8515

Special Issue Editors

Institute of Translational Pharmacology IFT, National Research Council of Italy (CNR), 00133 Rome, Italy
Interests: microRNAs; oxidative stress; cardiovascular diseases; Duchenne Muscular Distrophy; aging
Istituto Dermopatico dell’Immacolata- IDI-IRCCS
Interests: aging; skin,cancer; stem cells; skin regeneration; keratinocytes

Special Issue Information

Dear Colleagues,

Aging and different age-related diseases, such as cardiovascular disease, cancer, degenerative disorders, are characterized by a common feature, that is, an increase in oxidative stress and inflammation. This elicits different epigenetic changes, including the modulation of microRNAs.

Recently, microRNAs have been shown to be critical regulators of development, physiology, pathology and to be possible therapeutic targets. Besides microRNAs, alarmins, a class of proteins/peptides released in the extracellular space, play a major role as regulators of inflammation.

We invite investigators to contribute original research articles as well as review articles that address the molecular mechanisms and the current standing and progress in the area of microRNAs in oxidative stress and inflammation, with regard to aging and age-related diseases. We are interested in articles that explore the role of novel biomarkers, including microRNAs and alarmins, in oxidative stress and inflammation and the development of strategies to treat these pathologies. We hope this Special Issue will be of interest to biomedical investigators engaged in basic research as well as to those involved in clinical practice by providing new insights in aging mechanisms and helping envision treatments for age-related diseases.

Dr. Alessandra Magenta
Guest Editors
Dr. Elena Dellambra
Co-Guest Editor

Manuscript Submission Information

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Keywords

  • microRNAs
  • Alarmins
  • Oxidative stress
  • Inflammation
  • Age-related diseases

Published Papers (3 papers)

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Research

24 pages, 7710 KiB  
Article
miR-200c-3p Regulates Epitelial-to-Mesenchymal Transition in Epicardial Mesothelial Cells by Targeting Epicardial Follistatin-Related Protein 1
by Elena Pontemezzo, Eleonora Foglio, Enza Vernucci, Alessandra Magenta, Marco D’Agostino, Sara Sileno, Elena Astanina, Federico Bussolino, Laura Pellegrini, Antonia Germani, Matteo Antonio Russo and Federica Limana
Int. J. Mol. Sci. 2021, 22(9), 4971; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22094971 - 07 May 2021
Cited by 6 | Viewed by 2581
Abstract
Recent findings suggest that epithelial to mesenchymal transition (EMT), a key step during heart development, is involved in cardiac tissue repair following myocardial infarction (MI). MicroRNAs (miRNAs) act as key regulators in EMT processes; however, the mechanisms by which miRNAs target epicardial EMT [...] Read more.
Recent findings suggest that epithelial to mesenchymal transition (EMT), a key step during heart development, is involved in cardiac tissue repair following myocardial infarction (MI). MicroRNAs (miRNAs) act as key regulators in EMT processes; however, the mechanisms by which miRNAs target epicardial EMT remain largely unknown. Here, by using an in vitro model of epicardial EMT, we investigated the role of miRNAs as regulators of this process and their potential targets. EMT was induced in murine epicardial-mesothelial cells (EMCs) through TGF β1 treatment for 48, 72, and 96 h as indicated by the expression of EMT-related genes by qRT-PCR, WB, and immunofluorescence. Further, enhanced expression of stemness genes was also detected. Among several EMT-related miRNAs, miR-200c-3p expression resulted as the most strongly suppressed. Interestingly, we also found a significant upregulation of Follistatin-related protein 1 (FSTL1), a miR-200c predicted target already identified as a potent cardiogenic factor produced by epicardial cells that promotes regeneration following MI. Dual-luciferase reporter assay demonstrated that miR-200c-3p directly targeted the 3′-untranslated region of FSTL1 in EMCs. Consistently, WB analysis showed that knockdown of miR-200c-3p significantly increased FSTL1 expression, whereas overexpression of miR-200c-3p counteracted TGF β1-mediated FSTL1 upregulation. Importantly, FSTL1 silencing maintained epithelial features in EMCs, despite EMT induction by TGF β1, and attenuated EMT-associated traits, including migration and stemness. In conclusion, epicardial FSTL1, an important cardiogenic factor in its secreted form, induces EMT, stemness, and migration of EMCs in a miR-200c-3p dependent pathway. Full article
(This article belongs to the Special Issue Role of microRNAs and Alarmins in Aging and Age-Related Diseases)
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13 pages, 2081 KiB  
Article
The Nucleolar Protein Nucleophosmin Is Physiologically Secreted by Endothelial Cells in Response to Stress Exerting Proangiogenic Activity Both In Vitro and In Vivo
by Anna Di Carlo, Sara Beji, Silvia Palmerio, Mario Picozza, Marco D’Agostino, Vincenzo Petrozza, Roberta Melchionna, Antonia Germani, Alessandra Magenta, Elena De Falco and Daniele Avitabile
Int. J. Mol. Sci. 2021, 22(7), 3672; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22073672 - 01 Apr 2021
Cited by 5 | Viewed by 2033
Abstract
Nucleophosmin (NPM), a nucleolar multifunctional phosphoprotein, acts as a stress sensor in different cell types. NPM can be actively secreted by inflammatory cells, however its biology on endothelium remains unexplored. In this study, we show for the first time that NPM is secreted [...] Read more.
Nucleophosmin (NPM), a nucleolar multifunctional phosphoprotein, acts as a stress sensor in different cell types. NPM can be actively secreted by inflammatory cells, however its biology on endothelium remains unexplored. In this study, we show for the first time that NPM is secreted by human vein endothelial cells (HUVEC) in the early response to serum deprivation and that NPM acts as a pro-inflammatory and angiogenic molecule both in vitro and in vivo. Accordingly, 24 h of serum starvation condition induced NPM relocalization from the nucleus to cytoplasm. Interestingly, NPM was increasingly excreted in HUVEC-derived conditioned media in a time dependent fashion upon stress conditions up to 24 h. The secretion of NPM was unrelated to cell necrosis within 24 h. The treatment with exogenous and recombinant NPM (rNPM) enhanced migration as well as the Intercellular Adhesion Molecule 1 (ICAM-1) but not Vascular cell adhesion protein 1 (VCAM-1) expression and it did not affect cell proliferation. Notably, in vitro tube formation by Matrigel assay was significantly increased in HUVEC treated with rNPM compared to controls. This result was confirmed by the in vivo injection of Matrigel plug assay upon stimulation with rNPM, displaying significant enhanced number of functional capillaries in the plugs. The stimulation with rNPM in HUVEC was also associated to the increased expression of master genes regulating angiogenesis and migration, including Vascular Endothelial Growth Factor-A (VEGF-A), Hepatocyte Growth Factor (HGF), Stromal derived factor-1 (SDF-1), Fibroblast growth factor-2 (FGF-2), Platelet Derived Growth Factor-B (PDGF-B), and Matrix metallopeptidase 9 (MMP9). Our study demonstrates for the first time that NPM is physiologically secreted by somatic cells under stress condition and in the absence of cell necrosis. The analysis of the biological effects induced by NPM mainly related to a pro-angiogenic and inflammatory activity might suggest an important autocrine/paracrine role for NPM in the regulation of both phenomena. Full article
(This article belongs to the Special Issue Role of microRNAs and Alarmins in Aging and Age-Related Diseases)
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18 pages, 2903 KiB  
Article
Candidate Alzheimer’s Disease Biomarker miR-483-5p Lowers TAU Phosphorylation by Direct ERK1/2 Repression
by Siranjeevi Nagaraj, Andrew Want, Katarzyna Laskowska-Kaszub, Aleksandra Fesiuk, Sara Vaz, Elsa Logarinho and Urszula Wojda
Int. J. Mol. Sci. 2021, 22(7), 3653; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22073653 - 01 Apr 2021
Cited by 22 | Viewed by 3416
Abstract
MicroRNAs have been demonstrated as key regulators of gene expression in the etiology of a range of diseases including Alzheimer’s disease (AD). Recently, we identified miR-483-5p as the most upregulated miRNA amongst a panel of miRNAs in blood plasma specific to prodromal, early-stage [...] Read more.
MicroRNAs have been demonstrated as key regulators of gene expression in the etiology of a range of diseases including Alzheimer’s disease (AD). Recently, we identified miR-483-5p as the most upregulated miRNA amongst a panel of miRNAs in blood plasma specific to prodromal, early-stage Alzheimer’s disease patients. Here, we investigated the functional role of miR-483-5p in AD pathology. Using TargetScan and miRTarBase, we identified the microtubule-associated protein MAPT, often referred to as TAU, and the extracellular signal-regulated kinases 1 and 2 (ERK1 and ERK2), known to phosphorylate TAU, as predicted direct targets of miR-483-5p. Employing several functional assays, we found that miR-483-5p regulates ERK1 and ERK2 at both mRNA and protein levels, resulting in lower levels of phosphorylated forms of both kinases. Moreover, miR-483-5p-mediated repression of ERK1/2 resulted in reduced phosphorylation of TAU protein at epitopes associated with TAU neurofibrillary pathology in AD. These results indicate that upregulation of miR-483-5p can decrease phosphorylation of TAU via ERK pathway, representing a compensatory neuroprotective mechanism in AD pathology. This miR-483-5p/ERK1/TAU axis thus represents a novel target for intervention in AD. Full article
(This article belongs to the Special Issue Role of microRNAs and Alarmins in Aging and Age-Related Diseases)
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