The Impact of Melatonin and NLRP3 Inflammasome on the Expression of microRNAs in Aged Muscle
Muscular aging is a complex process and underlying physiological mechanisms are not fully clear. In recent years, the participation of the NF-kB pathway and the NLRP3 inflammasome in the chronic inflammation process that accompanies the skeletal muscle’s aging has been confirmed. microRNAs (miRs) fo...
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MDPI AG
2021-03-01
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author | Ramy KA Sayed Marisol Fernández-Ortiz José Fernández-Martínez Paula Aranda Martínez Ana Guerra-Librero César Rodríguez-Santana Tomás de Haro Germaine Escames Darío Acuña-Castroviejo Iryna Rusanova |
author_facet | Ramy KA Sayed Marisol Fernández-Ortiz José Fernández-Martínez Paula Aranda Martínez Ana Guerra-Librero César Rodríguez-Santana Tomás de Haro Germaine Escames Darío Acuña-Castroviejo Iryna Rusanova |
author_sort | Ramy KA Sayed |
collection | DOAJ |
description | Muscular aging is a complex process and underlying physiological mechanisms are not fully clear. In recent years, the participation of the NF-kB pathway and the NLRP3 inflammasome in the chronic inflammation process that accompanies the skeletal muscle’s aging has been confirmed. microRNAs (miRs) form part of a gene regulatory machinery, and they control numerous biological processes including inflammatory pathways. In this work, we studied the expression of four miRs; three of them are considered as inflammatory-related miRs (miR-21, miR-146a, and miR-223), and miR-483, which is related to the regulation of melatonin synthesis, among other targets. To investigate the changes of miRs expression in muscle along aging, the impact of inflammation, and the role of melatonin in aged skeletal muscle, we used the gastrocnemius muscle of wild type (WT) and NLRP3-knockout (NLRP3<sup>−</sup>) mice of 3, 12, and 24 months-old, with and without melatonin supplementation. The expression of miRs and pro-caspase-1, caspase-3, pro-IL-1β, bax, bcl-2, and p53, was investigated by qRT-PCR analysis. Histological examination of the gastrocnemius muscle was also done. The results showed that age increased the expression of miR-21 (<i>p</i> < 0.01), miR-146a, and miR-223 (<i>p</i> < 0.05, for both miRs) in WT mice, whereas the 24-months-old mutant mice revealed decline of miR-21 and miR-223 (<i>p</i> < 0.05), compared to WT age. The lack of NLRP3 inflammasome also improved the skeletal muscle fibers arrangement and reduced the collagen deposits compared with WT muscle during aging. For the first time, we showed that melatonin significantly reduced the expression of miR-21, miR-146a, and miR-223 (<i>p</i> < 0.05 for all ones, and <i>p</i> < 0.01 for miR-21 at 24 months old) in aged WT mice, increased miR-223 in NLRP3<sup>−</sup> mice (<i>p</i> < 0.05), and induced miR-483 expression in both mice strains, this increase being significant at 24 months of age. |
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spelling | doaj.art-d94cb5ddfce94be99abd30335ca2ba482023-11-21T13:04:36ZengMDPI AGAntioxidants2076-39212021-03-0110452410.3390/antiox10040524The Impact of Melatonin and NLRP3 Inflammasome on the Expression of microRNAs in Aged MuscleRamy KA Sayed0Marisol Fernández-Ortiz1José Fernández-Martínez2Paula Aranda Martínez3Ana Guerra-Librero4César Rodríguez-Santana5Tomás de Haro6Germaine Escames7Darío Acuña-Castroviejo8Iryna Rusanova9Department of Anatomy and Embryology, Faculty of Veterinary Medicine, Sohag University, Sohag 82524, EgyptCentro de Investigación Biomédica, Departamento de Fisiología, Facultad de Medicina, Instituto de Biotecnología, Parque Tecnológico de Ciencias de la Salud, Universidad de Granada, 18016 Granada, SpainCentro de Investigación Biomédica, Departamento de Fisiología, Facultad de Medicina, Instituto de Biotecnología, Parque Tecnológico de Ciencias de la Salud, Universidad de Granada, 18016 Granada, SpainCentro de Investigación Biomédica, Departamento de Fisiología, Facultad de Medicina, Instituto de Biotecnología, Parque Tecnológico de Ciencias de la Salud, Universidad de Granada, 18016 Granada, SpainCentro de Investigación Biomédica, Departamento de Fisiología, Facultad de Medicina, Instituto de Biotecnología, Parque Tecnológico de Ciencias de la Salud, Universidad de Granada, 18016 Granada, SpainCentro de Investigación Biomédica, Departamento de Fisiología, Facultad de Medicina, Instituto de Biotecnología, Parque Tecnológico de Ciencias de la Salud, Universidad de Granada, 18016 Granada, SpainUGC de Laboratorios Clínicos, Hospital Universitario San Cecilio, 18016 Granada, SpainCentro de Investigación Biomédica, Departamento de Fisiología, Facultad de Medicina, Instituto de Biotecnología, Parque Tecnológico de Ciencias de la Salud, Universidad de Granada, 18016 Granada, SpainCentro de Investigación Biomédica, Departamento de Fisiología, Facultad de Medicina, Instituto de Biotecnología, Parque Tecnológico de Ciencias de la Salud, Universidad de Granada, 18016 Granada, SpainCentro de Investigación Biomédica, Departamento de Fisiología, Facultad de Medicina, Instituto de Biotecnología, Parque Tecnológico de Ciencias de la Salud, Universidad de Granada, 18016 Granada, SpainMuscular aging is a complex process and underlying physiological mechanisms are not fully clear. In recent years, the participation of the NF-kB pathway and the NLRP3 inflammasome in the chronic inflammation process that accompanies the skeletal muscle’s aging has been confirmed. microRNAs (miRs) form part of a gene regulatory machinery, and they control numerous biological processes including inflammatory pathways. In this work, we studied the expression of four miRs; three of them are considered as inflammatory-related miRs (miR-21, miR-146a, and miR-223), and miR-483, which is related to the regulation of melatonin synthesis, among other targets. To investigate the changes of miRs expression in muscle along aging, the impact of inflammation, and the role of melatonin in aged skeletal muscle, we used the gastrocnemius muscle of wild type (WT) and NLRP3-knockout (NLRP3<sup>−</sup>) mice of 3, 12, and 24 months-old, with and without melatonin supplementation. The expression of miRs and pro-caspase-1, caspase-3, pro-IL-1β, bax, bcl-2, and p53, was investigated by qRT-PCR analysis. Histological examination of the gastrocnemius muscle was also done. The results showed that age increased the expression of miR-21 (<i>p</i> < 0.01), miR-146a, and miR-223 (<i>p</i> < 0.05, for both miRs) in WT mice, whereas the 24-months-old mutant mice revealed decline of miR-21 and miR-223 (<i>p</i> < 0.05), compared to WT age. The lack of NLRP3 inflammasome also improved the skeletal muscle fibers arrangement and reduced the collagen deposits compared with WT muscle during aging. For the first time, we showed that melatonin significantly reduced the expression of miR-21, miR-146a, and miR-223 (<i>p</i> < 0.05 for all ones, and <i>p</i> < 0.01 for miR-21 at 24 months old) in aged WT mice, increased miR-223 in NLRP3<sup>−</sup> mice (<i>p</i> < 0.05), and induced miR-483 expression in both mice strains, this increase being significant at 24 months of age.https://www.mdpi.com/2076-3921/10/4/524microRNAsmelatoninNLRP3 inflammasomeNF-kBaging |
spellingShingle | Ramy KA Sayed Marisol Fernández-Ortiz José Fernández-Martínez Paula Aranda Martínez Ana Guerra-Librero César Rodríguez-Santana Tomás de Haro Germaine Escames Darío Acuña-Castroviejo Iryna Rusanova The Impact of Melatonin and NLRP3 Inflammasome on the Expression of microRNAs in Aged Muscle Antioxidants microRNAs melatonin NLRP3 inflammasome NF-kB aging |
title | The Impact of Melatonin and NLRP3 Inflammasome on the Expression of microRNAs in Aged Muscle |
title_full | The Impact of Melatonin and NLRP3 Inflammasome on the Expression of microRNAs in Aged Muscle |
title_fullStr | The Impact of Melatonin and NLRP3 Inflammasome on the Expression of microRNAs in Aged Muscle |
title_full_unstemmed | The Impact of Melatonin and NLRP3 Inflammasome on the Expression of microRNAs in Aged Muscle |
title_short | The Impact of Melatonin and NLRP3 Inflammasome on the Expression of microRNAs in Aged Muscle |
title_sort | impact of melatonin and nlrp3 inflammasome on the expression of micrornas in aged muscle |
topic | microRNAs melatonin NLRP3 inflammasome NF-kB aging |
url | https://www.mdpi.com/2076-3921/10/4/524 |
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