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...

Full description

Bibliographic Details
Main Authors: 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
Format: Article
Language:English
Published: MDPI AG 2021-03-01
Series:Antioxidants
Subjects:
Online Access:https://www.mdpi.com/2076-3921/10/4/524
_version_ 1797539849111076864
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.
first_indexed 2024-03-10T12:51:43Z
format Article
id doaj.art-d94cb5ddfce94be99abd30335ca2ba48
institution Directory Open Access Journal
issn 2076-3921
language English
last_indexed 2024-03-10T12:51:43Z
publishDate 2021-03-01
publisher MDPI AG
record_format Article
series Antioxidants
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
work_keys_str_mv AT ramykasayed theimpactofmelatoninandnlrp3inflammasomeontheexpressionofmicrornasinagedmuscle
AT marisolfernandezortiz theimpactofmelatoninandnlrp3inflammasomeontheexpressionofmicrornasinagedmuscle
AT josefernandezmartinez theimpactofmelatoninandnlrp3inflammasomeontheexpressionofmicrornasinagedmuscle
AT paulaarandamartinez theimpactofmelatoninandnlrp3inflammasomeontheexpressionofmicrornasinagedmuscle
AT anaguerralibrero theimpactofmelatoninandnlrp3inflammasomeontheexpressionofmicrornasinagedmuscle
AT cesarrodriguezsantana theimpactofmelatoninandnlrp3inflammasomeontheexpressionofmicrornasinagedmuscle
AT tomasdeharo theimpactofmelatoninandnlrp3inflammasomeontheexpressionofmicrornasinagedmuscle
AT germaineescames theimpactofmelatoninandnlrp3inflammasomeontheexpressionofmicrornasinagedmuscle
AT darioacunacastroviejo theimpactofmelatoninandnlrp3inflammasomeontheexpressionofmicrornasinagedmuscle
AT irynarusanova theimpactofmelatoninandnlrp3inflammasomeontheexpressionofmicrornasinagedmuscle
AT ramykasayed impactofmelatoninandnlrp3inflammasomeontheexpressionofmicrornasinagedmuscle
AT marisolfernandezortiz impactofmelatoninandnlrp3inflammasomeontheexpressionofmicrornasinagedmuscle
AT josefernandezmartinez impactofmelatoninandnlrp3inflammasomeontheexpressionofmicrornasinagedmuscle
AT paulaarandamartinez impactofmelatoninandnlrp3inflammasomeontheexpressionofmicrornasinagedmuscle
AT anaguerralibrero impactofmelatoninandnlrp3inflammasomeontheexpressionofmicrornasinagedmuscle
AT cesarrodriguezsantana impactofmelatoninandnlrp3inflammasomeontheexpressionofmicrornasinagedmuscle
AT tomasdeharo impactofmelatoninandnlrp3inflammasomeontheexpressionofmicrornasinagedmuscle
AT germaineescames impactofmelatoninandnlrp3inflammasomeontheexpressionofmicrornasinagedmuscle
AT darioacunacastroviejo impactofmelatoninandnlrp3inflammasomeontheexpressionofmicrornasinagedmuscle
AT irynarusanova impactofmelatoninandnlrp3inflammasomeontheexpressionofmicrornasinagedmuscle