title: μ-Crystallin controls muscle function through thyroid hormone action.
abstract: μ-Crystallin (Crym), a thyroid hormone-binding protein, is abnormally up-regulated in the muscles of patients with facioscapulohumeral muscular dystrophy, a dominantly inherited progressive myopathy. However, the physiologic function of Crym in skeletal muscle remains to be elucidated. In this study, Crym was preferentially expressed in skeletal muscle throughout the body. Crym-knockout mice exhibited a significant hypertrophy of fast-twitch glycolytic type IIb fibers, causing an increase in grip strength and high intensity running ability in Crym-null mice. Genetic inactivation of Crym or blockade of Crym by siRNA-mediated knockdown up-regulated the gene expression of fast-glycolytic contractile fibers in satellite cell-derived myotubes in vitro These alterations in Crym-inactivated muscle were rescued by inhibition of thyroid hormone, even though Crym is a positive regulator of thyroid hormone action in nonmuscle cells. The results demonstrated that Crym is a crucial regulator of muscle plasticity, controlling metabolic and contractile properties of myofibers, and thus the selective inactivation of Crym may be a potential therapeutic target for muscle-wasting diseases, such as muscular dystrophies and age-related sarcopenia.-Seko, D., Ogawa, S., Li, T.-S., Taimura, A., Ono, Y. μ-Crystallin controls muscle function through thyroid hormone action.
authors.affiliation: Department of Stem Cell Biology, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, and Institute of Environmental Science, Graduate School of Fisheries and Environmental Sciences, Nagasaki, Japan.
authors.forename: Daiki
authors.initials: D
authors.lastname: Seko
authors.affiliation: Department of Stem Cell Biology, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, and.
authors.forename: Shizuka
authors.initials: S
authors.lastname: Ogawa
authors.affiliation: Department of Stem Cell Biology, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, and.
authors.forename: Tao-Sheng
authors.initials: TS
authors.lastname: Li
authors.affiliation: Institute of Environmental Science, Graduate School of Fisheries and Environmental Sciences, Nagasaki, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Taimura
authors.affiliation: Department of Stem Cell Biology, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, and yusuke-ono@nagasaki-u.ac.jp.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Ono
mesh_terms: D000818:Animals; D013956:Antithyroid Agents; D003459:Crystallins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000502:physiology*; D034622:RNA Interference; D034741:RNA, Small Interfering; D032496:Satellite Cells, Skeletal Muscle / Q000502:physiology*; D013974:Thyroxine / Q000235:genetics / Q000378:metabolism*; D014284:Triiodothyronine / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation; D000090803:mu-Crystallins
chemical_list: D013956:Antithyroid Agents; C000716470:Crym protein, mouse; D003459:Crystallins; D034741:RNA, Small Interfering; D014284:Triiodothyronine; D000090803:mu-Crystallins; D013974:Thyroxine
keywords: fiber type; muscle hypertrophy; muscle plasticity; skeletal muscle