Phenotype-Specific Response of Circulating miRNAs Provides New Biomarkers of Slow or Fast Muscle Damage

Skeletal muscle is a heterogeneous tissue composed of a continuum of contracting fibers ranging from slow-type to fast-type fibers. Muscle damage is a frequent event and a susceptibility of fast-fibers to exercise-induced damage (EIMD) or statins toxicity has been reported. Biological markers of mus...

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Main Authors: Julien Siracusa, Nathalie Koulmann, Antoine Sourdrille, Charles Chapus, Catherine Verret, Stéphanie Bourdon, Marie-Emmanuelle Goriot, Sébastien Banzet
Format: Article
Language:English
Published: Frontiers Media S.A. 2018-06-01
Series:Frontiers in Physiology
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fphys.2018.00684/full
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author Julien Siracusa
Nathalie Koulmann
Nathalie Koulmann
Antoine Sourdrille
Charles Chapus
Catherine Verret
Stéphanie Bourdon
Marie-Emmanuelle Goriot
Marie-Emmanuelle Goriot
Sébastien Banzet
Sébastien Banzet
Sébastien Banzet
author_facet Julien Siracusa
Nathalie Koulmann
Nathalie Koulmann
Antoine Sourdrille
Charles Chapus
Catherine Verret
Stéphanie Bourdon
Marie-Emmanuelle Goriot
Marie-Emmanuelle Goriot
Sébastien Banzet
Sébastien Banzet
Sébastien Banzet
author_sort Julien Siracusa
collection DOAJ
description Skeletal muscle is a heterogeneous tissue composed of a continuum of contracting fibers ranging from slow-type to fast-type fibers. Muscle damage is a frequent event and a susceptibility of fast-fibers to exercise-induced damage (EIMD) or statins toxicity has been reported. Biological markers of muscle damage such as creatine kinase (CK) are not fiber-type specific and new biomarkers are needed. Some microRNAs (miRNAs) are specific to the muscle tissue, can be found in the extracellular compartment and can rise in the plasma following muscle damage. Our aim was to identify whether a set of circulating miRNAs can be used as fiber-type specific biomarkers of muscle damage in a model of traumatic (crush) injuries induced either in the slow soleus (SOL) or in the fast extensor digitorum longus (EDL) muscles of rats. A subset of miRNAs composed of miR-1-3p, -133a-3p, -133b-3p, 206-3p, -208b-3p, 378a-3p, -434-3p, and -499-5p were measured by RT-PCR in non-injured SOL or EDL muscle and in the plasma of rats 12 h after damage induced to SOL or EDL. MiR-133b-3p, -378a-3p, and -434-3p were equally expressed both in SOL and EDL muscles. MiR-1-3-p and -133a-3p levels were higher in EDL compared to SOL (1.3- and 1.1-fold, respectively). Conversely, miR-206-3p, -208b-3p, and -499-5p were mainly expressed in SOL compared to EDL (7.4-, 35.4-, and 10.7-fold, respectively). In the plasma, miR-1-3p and -133a-3p were elevated following muscle damage compared to a control group, with no difference between SOL and EDL. MiR-133b-3p and -434-3p plasma levels were significantly higher in EDL compared to SOL (1.8- and 2.4-fold, respectively), while miR-378a-3p rose only in the EDL group. MiR-206-3p levels were elevated in SOL only (fourfold compared to EDL). Our results show that plasma miR-133b-3p and -434 are fast-fiber specific biomarkers, while miR-206-3p is a robust indicator of slow-fiber damage, opening new perspectives to monitor fiber-type selective muscle damage in research and clinic.
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spelling doaj.art-bd05c78ab6994dab985a89e6804c29c22022-12-21T17:30:44ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2018-06-01910.3389/fphys.2018.00684372246Phenotype-Specific Response of Circulating miRNAs Provides New Biomarkers of Slow or Fast Muscle DamageJulien Siracusa0Nathalie Koulmann1Nathalie Koulmann2Antoine Sourdrille3Charles Chapus4Catherine Verret5Stéphanie Bourdon6Marie-Emmanuelle Goriot7Marie-Emmanuelle Goriot8Sébastien Banzet9Sébastien Banzet10Sébastien Banzet11Unité de Physiologie de l’Exercice et des Activités en Conditions Extrêmes, Département Environnements Opérationnels, Institut de Recherche Biomédicale des Armées, Brétigny-sur-Orge, FranceUnité de Physiologie de l’Exercice et des Activités en Conditions Extrêmes, Département Environnements Opérationnels, Institut de Recherche Biomédicale des Armées, Brétigny-sur-Orge, FranceEcole du Val-de-Grâce, Paris, FranceUnité de Physiologie de l’Exercice et des Activités en Conditions Extrêmes, Département Environnements Opérationnels, Institut de Recherche Biomédicale des Armées, Brétigny-sur-Orge, FranceUnité de Biologie Moléculaire, Département des Plateformes et Recherche Technologique, Institut de Recherche Biomédicale des Armées, Brétigny-sur-Orge, FranceBureau de Gestion de Recherche Clinique, Institut de Recherche Biomédicale des Armées, Brétigny-sur-Orge, FranceUnité de Physiologie de l’Exercice et des Activités en Conditions Extrêmes, Département Environnements Opérationnels, Institut de Recherche Biomédicale des Armées, Brétigny-sur-Orge, FranceUnité de Thérapie Tissulaire et Traumatologie de Guerre, Département Soutien Médico-Chirurgical des Forces, Institut de Recherche Biomédicale des Armées, Brétigny-sur-Orge, FranceINSERM U 1197, Clamart, FranceEcole du Val-de-Grâce, Paris, FranceUnité de Thérapie Tissulaire et Traumatologie de Guerre, Département Soutien Médico-Chirurgical des Forces, Institut de Recherche Biomédicale des Armées, Brétigny-sur-Orge, FranceINSERM U 1197, Clamart, FranceSkeletal muscle is a heterogeneous tissue composed of a continuum of contracting fibers ranging from slow-type to fast-type fibers. Muscle damage is a frequent event and a susceptibility of fast-fibers to exercise-induced damage (EIMD) or statins toxicity has been reported. Biological markers of muscle damage such as creatine kinase (CK) are not fiber-type specific and new biomarkers are needed. Some microRNAs (miRNAs) are specific to the muscle tissue, can be found in the extracellular compartment and can rise in the plasma following muscle damage. Our aim was to identify whether a set of circulating miRNAs can be used as fiber-type specific biomarkers of muscle damage in a model of traumatic (crush) injuries induced either in the slow soleus (SOL) or in the fast extensor digitorum longus (EDL) muscles of rats. A subset of miRNAs composed of miR-1-3p, -133a-3p, -133b-3p, 206-3p, -208b-3p, 378a-3p, -434-3p, and -499-5p were measured by RT-PCR in non-injured SOL or EDL muscle and in the plasma of rats 12 h after damage induced to SOL or EDL. MiR-133b-3p, -378a-3p, and -434-3p were equally expressed both in SOL and EDL muscles. MiR-1-3-p and -133a-3p levels were higher in EDL compared to SOL (1.3- and 1.1-fold, respectively). Conversely, miR-206-3p, -208b-3p, and -499-5p were mainly expressed in SOL compared to EDL (7.4-, 35.4-, and 10.7-fold, respectively). In the plasma, miR-1-3p and -133a-3p were elevated following muscle damage compared to a control group, with no difference between SOL and EDL. MiR-133b-3p and -434-3p plasma levels were significantly higher in EDL compared to SOL (1.8- and 2.4-fold, respectively), while miR-378a-3p rose only in the EDL group. MiR-206-3p levels were elevated in SOL only (fourfold compared to EDL). Our results show that plasma miR-133b-3p and -434 are fast-fiber specific biomarkers, while miR-206-3p is a robust indicator of slow-fiber damage, opening new perspectives to monitor fiber-type selective muscle damage in research and clinic.https://www.frontiersin.org/article/10.3389/fphys.2018.00684/fullbiomarkerscirculating miRNAsmuscle damagemuscle fiber typeratEIMD
spellingShingle Julien Siracusa
Nathalie Koulmann
Nathalie Koulmann
Antoine Sourdrille
Charles Chapus
Catherine Verret
Stéphanie Bourdon
Marie-Emmanuelle Goriot
Marie-Emmanuelle Goriot
Sébastien Banzet
Sébastien Banzet
Sébastien Banzet
Phenotype-Specific Response of Circulating miRNAs Provides New Biomarkers of Slow or Fast Muscle Damage
Frontiers in Physiology
biomarkers
circulating miRNAs
muscle damage
muscle fiber type
rat
EIMD
title Phenotype-Specific Response of Circulating miRNAs Provides New Biomarkers of Slow or Fast Muscle Damage
title_full Phenotype-Specific Response of Circulating miRNAs Provides New Biomarkers of Slow or Fast Muscle Damage
title_fullStr Phenotype-Specific Response of Circulating miRNAs Provides New Biomarkers of Slow or Fast Muscle Damage
title_full_unstemmed Phenotype-Specific Response of Circulating miRNAs Provides New Biomarkers of Slow or Fast Muscle Damage
title_short Phenotype-Specific Response of Circulating miRNAs Provides New Biomarkers of Slow or Fast Muscle Damage
title_sort phenotype specific response of circulating mirnas provides new biomarkers of slow or fast muscle damage
topic biomarkers
circulating miRNAs
muscle damage
muscle fiber type
rat
EIMD
url https://www.frontiersin.org/article/10.3389/fphys.2018.00684/full
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