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μ‐Crystallin controls muscle function through thyroid hormone action
Author(s) -
Seko Daiki,
Ogawa Shizuka,
Li TaoSheng,
Taimura Akihiro,
Ono Yusuke
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.15-280933
Subject(s) - medicine , endocrinology , skeletal muscle , myogenesis , thyroid , myopathy , muscular dystrophy , hormone , myocyte , gene knockdown , biology , muscle hypertrophy , thyroid hormone receptor beta , thyroid hormone receptor , chemistry , gene , biochemistry , hormone receptor , cancer , breast cancer
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. FASEB J. 30, 1733–1740 (2016). www.fasebj.org