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Eccentric Resistance Training Ameliorates Muscle Weakness in a Mouse Model of Idiopathic Inflammatory Myopathies
Author(s) -
Himori Koichi,
Ashida Yuki,
Tatebayashi Daisuke,
Abe Masami,
Saito Yuki,
Chikenji Takako,
Westerblad Håkan,
Andersson Daniel C.,
Yamada Takashi
Publication year - 2021
Publication title -
arthritis and rheumatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.106
H-Index - 314
eISSN - 2326-5205
pISSN - 2326-5191
DOI - 10.1002/art.41594
Subject(s) - myositis , endoplasmic reticulum , myofibril , myosin , ankle , muscle weakness , inflammation , eccentric , medicine , endocrinology , chemistry , myopathy , weakness , gastrocnemius muscle , pathology , anatomy , skeletal muscle , biochemistry , physics , quantum mechanics
Objective High‐force eccentric contractions (ECCs) have traditionally been excluded from rehabilitation programs that include patients with idiopathic inflammatory myopathies (IIMs) due to unverified fear of causing muscle damage and inflammation. In an IIM animal model that used mice with experimental autoimmune myositis (EAM), we undertook this study to investigate whether ECC training can safely and effectively be used to counteract muscle weakness in IIM. Methods EAM was induced in BALB/c mice by immunization with 3 injections of myosin emulsified in Freund’s complete adjuvant. Controls (n = 12) and mice with EAM (n = 12) were exposed to either an acute bout of 100 ECCs or 4 weeks of ECC training (20 ECCs every other day). To induce ECCs, plantar flexor muscles were electrically stimulated while the ankle was forcibly dorsiflexed. Results Less cell damage, as assessed by Evans blue dye uptake, was observed in the muscles of mice with EAM, compared to controls, after an acute bout of 100 ECCs ( P < 0.05). Maximum Ca 2+ ‐activated force was decreased in skinned gastrocnemius muscle fibers from mice with EAM, and this was accompanied by increased expression of endoplasmic reticulum (ER) stress proteins, including Gsp78 and Gsp94 ( P < 0.05). ECC training prevented the decrease in force and the increase in ER stress proteins and also enhanced the expression and myofibrillar binding of small heat‐shock proteins (HSPs) ( P < 0.05), which can stabilize myofibrillar structure and function. Conclusion ECC training protected against the reduction in myofibrillar force–generating capacity in an IIM mouse model, and this occurred via inhibition of ER stress responses and small HSP–mediated myofibrillar stabilization.