Can Be miR-126-3p a Biomarker of Premature Aging? An Ex Vivo and In Vitro Study in Fabry Disease
Fabry disease (FD) is a lysosomal storage disorder (LSD) characterized by lysosomal accumulation of glycosphingolipids in a wide variety of cytotypes, including endothelial cells (ECs). FD patients experience a significantly reduced life expectancy compared to the general population; therefore, the...
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MDPI AG
2021-02-01
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author | Alessia Lo Curto Simona Taverna Maria Assunta Costa Rosa Passantino Giuseppa Augello Giorgia Adamo Anna Aiello Paolo Colomba Carmela Zizzo Marco Zora Giulia Accardi Giuseppina Candore Daniele Francofonte Tiziana Di Chiara Riccardo Alessandro Calogero Caruso Giovanni Duro Giuseppe Cammarata |
author_facet | Alessia Lo Curto Simona Taverna Maria Assunta Costa Rosa Passantino Giuseppa Augello Giorgia Adamo Anna Aiello Paolo Colomba Carmela Zizzo Marco Zora Giulia Accardi Giuseppina Candore Daniele Francofonte Tiziana Di Chiara Riccardo Alessandro Calogero Caruso Giovanni Duro Giuseppe Cammarata |
author_sort | Alessia Lo Curto |
collection | DOAJ |
description | Fabry disease (FD) is a lysosomal storage disorder (LSD) characterized by lysosomal accumulation of glycosphingolipids in a wide variety of cytotypes, including endothelial cells (ECs). FD patients experience a significantly reduced life expectancy compared to the general population; therefore, the association with a premature aging process would be plausible. To assess this hypothesis, miR-126-3p, a senescence-associated microRNA (SA-miRNAs), was considered as an aging biomarker. The levels of miR-126-3p contained in small extracellular vesicles (sEVs), with about 130 nm of diameter, were measured in FD patients and healthy subjects divided into age classes, in vitro, in human umbilical vein endothelial cells (HUVECs) “young” and undergoing replicative senescence, through a quantitative polymerase chain reaction (qPCR) approach. We confirmed that, in vivo, circulating miR-126 levels physiologically increase with age. In vitro, miR-126 augments in HUVECs underwent replicative senescence. We observed that FD patients are characterized by higher miR-126-3p levels in sEVs, compared to age-matched healthy subjects. We also explored, in vitro, the effect on ECs of glycosphingolipids that are typically accumulated in FD patients. We observed that FD storage substances induced in HUVECs premature senescence and increased of miR-126-3p levels. This study reinforces the hypothesis that FD may aggravate the normal aging process. |
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language | English |
last_indexed | 2024-03-09T05:00:32Z |
publishDate | 2021-02-01 |
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series | Cells |
spelling | doaj.art-dd46536a03144ca6961649a8754ef2722023-12-03T13:01:12ZengMDPI AGCells2073-44092021-02-0110235610.3390/cells10020356Can Be miR-126-3p a Biomarker of Premature Aging? An Ex Vivo and In Vitro Study in Fabry DiseaseAlessia Lo Curto0Simona Taverna1Maria Assunta Costa2Rosa Passantino3Giuseppa Augello4Giorgia Adamo5Anna Aiello6Paolo Colomba7Carmela Zizzo8Marco Zora9Giulia Accardi10Giuseppina Candore11Daniele Francofonte12Tiziana Di Chiara13Riccardo Alessandro14Calogero Caruso15Giovanni Duro16Giuseppe Cammarata17Institute for Research and Biomedical Innovation (IRIB), National Research Council (CNR), 90146 Palermo, ItalyInstitute for Research and Biomedical Innovation (IRIB), National Research Council (CNR), 90146 Palermo, ItalyInstitute of Byophysics, National Research Council (CNR), 90146 Palermo, ItalyInstitute of Byophysics, National Research Council (CNR), 90146 Palermo, ItalyInstitute for Research and Biomedical Innovation (IRIB), National Research Council (CNR), 90146 Palermo, ItalyInstitute for Research and Biomedical Innovation (IRIB), National Research Council (CNR), 90146 Palermo, ItalyLaboratory of Immunopathology and Immunosenescence, Department of Biomedicine, Neuroscience and Advanced Diagnostics, University of Palermo, 90134 Palermo, ItalyInstitute for Research and Biomedical Innovation (IRIB), National Research Council (CNR), 90146 Palermo, ItalyInstitute for Research and Biomedical Innovation (IRIB), National Research Council (CNR), 90146 Palermo, ItalyInstitute for Research and Biomedical Innovation (IRIB), National Research Council (CNR), 90146 Palermo, ItalyLaboratory of Immunopathology and Immunosenescence, Department of Biomedicine, Neuroscience and Advanced Diagnostics, University of Palermo, 90134 Palermo, ItalyLaboratory of Immunopathology and Immunosenescence, Department of Biomedicine, Neuroscience and Advanced Diagnostics, University of Palermo, 90134 Palermo, ItalyInstitute for Research and Biomedical Innovation (IRIB), National Research Council (CNR), 90146 Palermo, ItalyDepartment PROMISE, School of Medicine, University of Palermo, 90127 Palermo, ItalyInstitute for Research and Biomedical Innovation (IRIB), National Research Council (CNR), 90146 Palermo, ItalyLaboratory of Immunopathology and Immunosenescence, Department of Biomedicine, Neuroscience and Advanced Diagnostics, University of Palermo, 90134 Palermo, ItalyInstitute for Research and Biomedical Innovation (IRIB), National Research Council (CNR), 90146 Palermo, ItalyInstitute for Research and Biomedical Innovation (IRIB), National Research Council (CNR), 90146 Palermo, ItalyFabry disease (FD) is a lysosomal storage disorder (LSD) characterized by lysosomal accumulation of glycosphingolipids in a wide variety of cytotypes, including endothelial cells (ECs). FD patients experience a significantly reduced life expectancy compared to the general population; therefore, the association with a premature aging process would be plausible. To assess this hypothesis, miR-126-3p, a senescence-associated microRNA (SA-miRNAs), was considered as an aging biomarker. The levels of miR-126-3p contained in small extracellular vesicles (sEVs), with about 130 nm of diameter, were measured in FD patients and healthy subjects divided into age classes, in vitro, in human umbilical vein endothelial cells (HUVECs) “young” and undergoing replicative senescence, through a quantitative polymerase chain reaction (qPCR) approach. We confirmed that, in vivo, circulating miR-126 levels physiologically increase with age. In vitro, miR-126 augments in HUVECs underwent replicative senescence. We observed that FD patients are characterized by higher miR-126-3p levels in sEVs, compared to age-matched healthy subjects. We also explored, in vitro, the effect on ECs of glycosphingolipids that are typically accumulated in FD patients. We observed that FD storage substances induced in HUVECs premature senescence and increased of miR-126-3p levels. This study reinforces the hypothesis that FD may aggravate the normal aging process.https://www.mdpi.com/2073-4409/10/2/356Fabry diseasemicroRNAmiR-126-3psmall extracellular vesiclesagingsenescence |
spellingShingle | Alessia Lo Curto Simona Taverna Maria Assunta Costa Rosa Passantino Giuseppa Augello Giorgia Adamo Anna Aiello Paolo Colomba Carmela Zizzo Marco Zora Giulia Accardi Giuseppina Candore Daniele Francofonte Tiziana Di Chiara Riccardo Alessandro Calogero Caruso Giovanni Duro Giuseppe Cammarata Can Be miR-126-3p a Biomarker of Premature Aging? An Ex Vivo and In Vitro Study in Fabry Disease Cells Fabry disease microRNA miR-126-3p small extracellular vesicles aging senescence |
title | Can Be miR-126-3p a Biomarker of Premature Aging? An Ex Vivo and In Vitro Study in Fabry Disease |
title_full | Can Be miR-126-3p a Biomarker of Premature Aging? An Ex Vivo and In Vitro Study in Fabry Disease |
title_fullStr | Can Be miR-126-3p a Biomarker of Premature Aging? An Ex Vivo and In Vitro Study in Fabry Disease |
title_full_unstemmed | Can Be miR-126-3p a Biomarker of Premature Aging? An Ex Vivo and In Vitro Study in Fabry Disease |
title_short | Can Be miR-126-3p a Biomarker of Premature Aging? An Ex Vivo and In Vitro Study in Fabry Disease |
title_sort | can be mir 126 3p a biomarker of premature aging an ex vivo and in vitro study in fabry disease |
topic | Fabry disease microRNA miR-126-3p small extracellular vesicles aging senescence |
url | https://www.mdpi.com/2073-4409/10/2/356 |
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