Ectopic expression of myostatin induces atrophy of adult skeletal muscle by decreasing muscle gene expression
Autor: | Catherine Mouret, Marielle Pasdeloup, Damien Freyssenet, Régis Bonnefoy, André Peinnequin, Anne-Cécile Durieux, Adel Amirouche, Nathalie Koulmann, Xavier Bigard, Sébastien Banzet |
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Přispěvatelé: | Laboratoire de Physiologie et physiopathologie de l'exercice et handicap (LPPEH), Université Jean Monnet [Saint-Étienne] (UJM), Institute of Anatomy, University of Berne, Département des Facteurs Humains, Service de Santé des Armées-Ministère de la Défense, Département de Radiobiologie et Radiopathologie, Sinniger, Valérie, Universität Bern [Bern] (UNIBE) |
Rok vydání: | 2007 |
Předmět: |
Male
Time Factors Caveolin 3 Muscle Fibers Skeletal Myostatin MESH: Rats Sprague-Dawley Muscle Development Rats Sprague-Dawley 0302 clinical medicine Endocrinology MESH: Genetic Vectors Transforming Growth Factor beta MESH: Reverse Transcriptase Polymerase Chain Reaction Myosin MESH: Animals MESH: Caveolin 3 0303 health sciences MESH: Muscle Skeletal MESH: Muscle Fibers Skeletal biology MESH: Immunoblotting Myogenesis Reverse Transcriptase Polymerase Chain Reaction RNA-Binding Proteins MESH: Transcription Factors musculoskeletal system MESH: Gene Expression Regulation Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha Muscle atrophy Muscular Atrophy medicine.anatomical_structure MESH: Muscle Development Myogenin medicine.symptom medicine.medical_specialty MESH: Rats Genetic Vectors Immunoblotting MESH: Myogenin MESH: Myostatin 03 medical and health sciences Internal medicine Myokine [SDV.BBM] Life Sciences [q-bio]/Biochemistry Molecular Biology medicine Animals [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology RNA Messenger Muscle Skeletal MESH: Transforming Growth Factor beta 030304 developmental biology MESH: RNA Messenger MyoD Protein MESH: MyoD Protein MESH: Time Factors MESH: Muscular Atrophy Skeletal muscle MESH: Male Rats MESH: RNA-Binding Proteins Gene Expression Regulation GDF11 biology.protein 030217 neurology & neurosurgery Transcription Factors |
Zdroj: | Endocrinology Endocrinology, Endocrine Society, 2007, 148 (7), pp.3140-7. ⟨10.1210/en.2006-1500⟩ |
ISSN: | 0013-7227 |
DOI: | 10.1210/en.2006-1500⟩ |
Popis: | International audience; Myostatin is a master regulator of myogenesis and early postnatal skeletal muscle growth. However, myostatin has been also involved in several forms of muscle wasting in adulthood, suggesting a functional role for myostatin in the regulation of skeletal muscle mass in adult. In the present study, localized ectopic expression of myostatin was achieved by gene electrotransfer of a myostatin expression vector into the tibialis anterior muscle of adult Sprague Dawley male rats. The corresponding empty vector was electrotransfected in contralateral muscle. Ectopic myostatin mRNA was abundantly present in muscles electrotransfected with myostatin expression vector, whereas it was undetectable in contralateral muscles. Overexpression of myostatin elicited a significant decrease in muscle mass (10 and 20% reduction 7 and 14 d after gene electrotransfer, respectively), muscle fiber cross-sectional area (15 and 30% reduction 7 and 14 d after gene electrotransfer, respectively), and muscle protein content (20% reduction). No decrease in fiber number was observed. Overexpression of myostatin markedly decreased the expression of muscle structural genes (myosin heavy chain IIb, troponin I, and desmin) and the expression of myogenic transcription factors (MyoD and myogenin). Incidentally, mRNA level of caveolin-3 and peroxisome proliferator activated receptor gamma coactivator-1alpha was also significantly decreased 14 d after myostatin gene electrotransfer. To conclude, our study demonstrates that myostatin-induced muscle atrophy elicits the down-regulation of muscle-specific gene expression. Our observations support an important role for myostatin in muscle atrophy in physiological and physiopathological situations where myostatin expression is induced. |
Databáze: | OpenAIRE |
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