Circulating myomiRs in Muscle Denervation: From Surgical to ALS Pathological Condition
Irene Casola,
Bianca Maria Scicchitano,
Elisa Lepore,
Silvia Mandillo,
Elisabetta Golini,
Carmine Nicoletti,
Laura Barberi,
Gabriella Dobrowolny,
Antonio Musarò
Affiliations
Irene Casola
Laboratory Affiliated to Istituto Pasteur Italia—Fondazione Cenci Bolognetti, DAHFMO-Unit of Histology and Medical Embryology, Sapienza University of Rome, Via A. Scarpa, 14, 00161 Rome, Italy
Bianca Maria Scicchitano
Sezione di Istologia ed Embriologia, Dipartimento di Scienze della Vita e Sanità Pubblica, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Roma, Italy
Elisa Lepore
Laboratory Affiliated to Istituto Pasteur Italia—Fondazione Cenci Bolognetti, DAHFMO-Unit of Histology and Medical Embryology, Sapienza University of Rome, Via A. Scarpa, 14, 00161 Rome, Italy
Silvia Mandillo
Institute of Biochemistry and Cell Biology, National Research Council, Monterotondo scalo, 00015 Rome, Italy
Elisabetta Golini
Institute of Biochemistry and Cell Biology, National Research Council, Monterotondo scalo, 00015 Rome, Italy
Carmine Nicoletti
Laboratory Affiliated to Istituto Pasteur Italia—Fondazione Cenci Bolognetti, DAHFMO-Unit of Histology and Medical Embryology, Sapienza University of Rome, Via A. Scarpa, 14, 00161 Rome, Italy
Laura Barberi
Laboratory Affiliated to Istituto Pasteur Italia—Fondazione Cenci Bolognetti, DAHFMO-Unit of Histology and Medical Embryology, Sapienza University of Rome, Via A. Scarpa, 14, 00161 Rome, Italy
Gabriella Dobrowolny
Laboratory Affiliated to Istituto Pasteur Italia—Fondazione Cenci Bolognetti, DAHFMO-Unit of Histology and Medical Embryology, Sapienza University of Rome, Via A. Scarpa, 14, 00161 Rome, Italy
Antonio Musarò
Laboratory Affiliated to Istituto Pasteur Italia—Fondazione Cenci Bolognetti, DAHFMO-Unit of Histology and Medical Embryology, Sapienza University of Rome, Via A. Scarpa, 14, 00161 Rome, Italy
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.
