The Impact of Melatonin and NLRP3 Inflammasome on the Expression of microRNAs in Aged Muscle
Metadata
Show full item recordAuthor
Sayed, Ramy K. A.; Fernández Ortiz, Marisol; Fernández Martínez, José; Aranda Martínez, Paula; Guerra Librero Rite, Ana; Rodríguez Santana, César; Escames Rosa, Germaine; Acuña Castroviejo, Darío; Rusanova Rusanova, IrynaEditorial
MDPI
Materia
MicroRNAs Melatonin NLRP3-inflammasome NF-KB Aging
Date
2021Referencia bibliográfica
Sayed, R.K.; FernándezOrtiz, M.; Fernández-Martínez, J.; Aranda Martínez, P.; Guerra-Librero, A.; Rodríguez-Santana, C.; de Haro, T.; Escames, G.; Acuña-Castroviejo, D.; Rusanova, I. The Impact of Melatonin and NLRP3 Inflammasome on the Expression of microRNAs in Aged Muscle. Antioxidants 2021, 10, 524. https://doi.org/10.3390/ antiox10040524
Sponsorship
Instituto de Salud Carlos III (Ministerio de Economía y Competitividad, Spain); European Regional Development Fund/European Social Fund; Consejería de Innovación, Ciencia y Empresa, Junta de Andalucía (CTS-101); FPU fellowships from the Ministerio de EducaciónAbstract
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−) 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 (p < 0.01), miR-146a, and miR-223 (p < 0.05,
for both miRs) in WT mice, whereas the 24-months-old mutant mice revealed decline of miR-21
and miR-223 (p < 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 (p < 0.05 for all ones, and p < 0.01 for miR-21 at 24 months old) in
aged WT mice, increased miR-223 in NLRP3− mice (p < 0.05), and induced miR-483 expression in
both mice strains, this increase being significant at 24 months of age.