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Circulating myomiRs in Muscle Denervation: From Surgical to ALS Pathological Condition

ALS is a fatal neurodegenerative disease that is associated with muscle atrophy, motoneuron degeneration and denervation. Different mechanisms have been proposed to explain the pathogenesis of the disease; in this context, microRNAs have been described as biomarkers and potential pathogenetic factor...

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Autores principales: Casola, Irene, Scicchitano, Bianca Maria, Lepore, Elisa, Mandillo, Silvia, Golini, Elisabetta, Nicoletti, Carmine, Barberi, Laura, Dobrowolny, Gabriella, Musarò, Antonio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8393851/
https://www.ncbi.nlm.nih.gov/pubmed/34440812
http://dx.doi.org/10.3390/cells10082043
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author Casola, Irene
Scicchitano, Bianca Maria
Lepore, Elisa
Mandillo, Silvia
Golini, Elisabetta
Nicoletti, Carmine
Barberi, Laura
Dobrowolny, Gabriella
Musarò, Antonio
author_facet Casola, Irene
Scicchitano, Bianca Maria
Lepore, Elisa
Mandillo, Silvia
Golini, Elisabetta
Nicoletti, Carmine
Barberi, Laura
Dobrowolny, Gabriella
Musarò, Antonio
author_sort Casola, Irene
collection PubMed
description ALS is a fatal neurodegenerative disease that is associated with muscle atrophy, motoneuron degeneration and denervation. Different mechanisms have been proposed to explain the pathogenesis of the disease; in this context, microRNAs have been described as biomarkers and potential pathogenetic factors for ALS. MyomiRs are microRNAs produced by skeletal muscle, and they play an important role in tissue homeostasis; moreover, they can be released in blood circulation in pathological conditions, including ALS. However, the functional role of myomiRs in muscle denervation has not yet been fully clarified. In this study, we analyze the levels of two myomiRs, namely miR-206 and miR-133a, in skeletal muscle and blood samples of denervated mice, and we demonstrate that surgical denervation reduces the expression of both miR-206 and miR-133a, while miR-206 but not miR-133a is upregulated during the re-innervation process. Furthermore, we quantify the levels of miR-206 and miR-133a in serum samples of two ALS mouse models, characterized by different disease velocities, and we demonstrate a different modulation of circulating myomiRs during ALS disease, according to the velocity of disease progression. Moreover, taking into account surgical and pathological denervation, we describe a different response to increasing amounts of circulating miR-206, suggesting a hormetic effect of miR-206 in relation to changes in neuromuscular communication.
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spelling pubmed-83938512021-08-28 Circulating myomiRs in Muscle Denervation: From Surgical to ALS Pathological Condition Casola, Irene Scicchitano, Bianca Maria Lepore, Elisa Mandillo, Silvia Golini, Elisabetta Nicoletti, Carmine Barberi, Laura Dobrowolny, Gabriella Musarò, Antonio Cells Article ALS is a fatal neurodegenerative disease that is associated with muscle atrophy, motoneuron degeneration and denervation. Different mechanisms have been proposed to explain the pathogenesis of the disease; in this context, microRNAs have been described as biomarkers and potential pathogenetic factors for ALS. MyomiRs are microRNAs produced by skeletal muscle, and they play an important role in tissue homeostasis; moreover, they can be released in blood circulation in pathological conditions, including ALS. However, the functional role of myomiRs in muscle denervation has not yet been fully clarified. In this study, we analyze the levels of two myomiRs, namely miR-206 and miR-133a, in skeletal muscle and blood samples of denervated mice, and we demonstrate that surgical denervation reduces the expression of both miR-206 and miR-133a, while miR-206 but not miR-133a is upregulated during the re-innervation process. Furthermore, we quantify the levels of miR-206 and miR-133a in serum samples of two ALS mouse models, characterized by different disease velocities, and we demonstrate a different modulation of circulating myomiRs during ALS disease, according to the velocity of disease progression. Moreover, taking into account surgical and pathological denervation, we describe a different response to increasing amounts of circulating miR-206, suggesting a hormetic effect of miR-206 in relation to changes in neuromuscular communication. MDPI 2021-08-10 /pmc/articles/PMC8393851/ /pubmed/34440812 http://dx.doi.org/10.3390/cells10082043 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Casola, Irene
Scicchitano, Bianca Maria
Lepore, Elisa
Mandillo, Silvia
Golini, Elisabetta
Nicoletti, Carmine
Barberi, Laura
Dobrowolny, Gabriella
Musarò, Antonio
Circulating myomiRs in Muscle Denervation: From Surgical to ALS Pathological Condition
title Circulating myomiRs in Muscle Denervation: From Surgical to ALS Pathological Condition
title_full Circulating myomiRs in Muscle Denervation: From Surgical to ALS Pathological Condition
title_fullStr Circulating myomiRs in Muscle Denervation: From Surgical to ALS Pathological Condition
title_full_unstemmed Circulating myomiRs in Muscle Denervation: From Surgical to ALS Pathological Condition
title_short Circulating myomiRs in Muscle Denervation: From Surgical to ALS Pathological Condition
title_sort circulating myomirs in muscle denervation: from surgical to als pathological condition
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8393851/
https://www.ncbi.nlm.nih.gov/pubmed/34440812
http://dx.doi.org/10.3390/cells10082043
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