Open this publication in new window or tab >>Örebro University, School of Health Sciences. Molecular Muscle Physiology and Pathophysiology, Department of Physiology and Pharmacology, Karolinska Institutet, Biomedicum, Stockholm, Sweden.
Molecular & Cellular Exercise Physiology, Department of Physiology and Pharmacology, Karolinska Institutet, Biomedicum, Stockholm, Sweden.
Molecular & Cellular Exercise Physiology, Department of Physiology and Pharmacology, Karolinska Institutet, Biomedicum, Stockholm, Sweden.
Molecular & Cellular Exercise Physiology, Department of Physiology and Pharmacology, Karolinska Institutet, Biomedicum, Stockholm, Sweden; Karp Research Building, Boston, MA, USA.
Molecular & Cellular Exercise Physiology, Department of Physiology and Pharmacology, Karolinska Institutet, Biomedicum, Stockholm, Sweden.
Molecular & Cellular Exercise Physiology, Department of Physiology and Pharmacology, Karolinska Institutet, Biomedicum, Stockholm, Sweden.
Molecular & Cellular Exercise Physiology, Department of Physiology and Pharmacology, Karolinska Institutet, Biomedicum, Stockholm, Sweden.
Molecular & Cellular Exercise Physiology, Department of Physiology and Pharmacology, Karolinska Institutet, Biomedicum, Stockholm, Sweden.
Division of Cardiovascular and Metabolic Disease, Institut de recherches cliniques de Montreal (IRCM), Montreal, QC, Canada.
Division of Endocrinology, Diabetes and Nutrition, Mayo Clinic, Rochester, MN, USA.
Division of Endocrinology, Diabetes and Nutrition, Mayo Clinic, Rochester, MN, USA.
Molecular Muscle Physiology and Pathophysiology, Department of Physiology and Pharmacology, Karolinska Institutet, Biomedicum, Stockholm, Sweden.
Molecular & Cellular Exercise Physiology, Department of Physiology and Pharmacology, Karolinska Institutet, Biomedicum, Stockholm, Sweden.
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2019 (English)In: Skeletal Muscle, ISSN 2044-5040, Vol. 9, no 1, article id 26Article in journal (Refereed) Published
Abstract [en]
BACKGROUND: Skeletal muscle mass and strength are crucial determinants of health. Muscle mass loss is associated with weakness, fatigue, and insulin resistance. In fact, it is predicted that controlling muscle atrophy can reduce morbidity and mortality associated with diseases such as cancer cachexia and sarcopenia.
METHODS: release in individual fibers. Finally, to explore the relationship between LMCD1 and calcineurin, we ectopically expressed Lmcd1 in the gastrocnemius muscle and treated those mice with cyclosporine A (calcineurin inhibitor). In addition, we used a luciferase reporter construct containing the myoregulin gene promoter to confirm the role of a LMCD1-calcineurin-myoregulin axis in skeletal muscle mass control and calcium handling.
RESULTS: Here, we identify LIM and cysteine-rich domains 1 (LMCD1) as a positive regulator of muscle mass, that increases muscle protein synthesis and fiber size. LMCD1 expression in vivo was sufficient to increase specific force with lower requirement for calcium handling and to reduce muscle fatigue. Conversely, silencing LMCD1 expression impairs calcium handling and force, and induces muscle fatigue without overt atrophy. The actions of LMCD1 were dependent on calcineurin, as its inhibition using cyclosporine A reverted the observed hypertrophic phenotype. Finally, we determined that LMCD1 represses the expression of myoregulin, a known negative regulator of muscle performance. Interestingly, we observed that skeletal muscle LMCD1 expression is reduced in patients with skeletal muscle disease.
CONCLUSIONS: handling, and fatigue resistance. This work uncovers a novel role for LMCD1 in the regulation of skeletal muscle mass and function with potential therapeutic implications.
Place, publisher, year, edition, pages
BioMed Central, 2019
Keywords
Calcineurin, Calcium, Force, Hypertrophy, LMCD1, Skeletal muscle
National Category
Physiology
Identifiers
urn:nbn:se:oru:diva-77713 (URN)10.1186/s13395-019-0214-1 (DOI)31666122 (PubMedID)
2019-11-072019-11-072019-11-07Bibliographically approved