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Open AccessArticle

Transthyretin Maintains Muscle Homeostasis through the Novel Shuttle Pathway of Thyroid Hormones during Myoblast Differentiation

1
Department of Medical Biotechnology, Yeungnam University, Gyeongsan 38541, Korea
2
Department of Biomedical Science, Daegu Catholic University, Gyeongsan 38430, Korea
3
College of Veterinary Medicine, Kyungpook National University, Daegu 41566, Korea
4
Department of Physiology, College of Medicine, Yeungnam University, Daegu 42415, Korea
*
Author to whom correspondence should be addressed.
These two authors contributed equally to this work.
Cells 2019, 8(12), 1565; https://doi.org/10.3390/cells8121565
Received: 8 October 2019 / Revised: 13 November 2019 / Accepted: 2 December 2019 / Published: 4 December 2019
Skeletal muscle, the largest part of the total body mass, influences energy and protein metabolism as well as maintaining homeostasis. Herein, we demonstrate that during murine muscle satellite cell and myoblast differentiation, transthyretin (TTR) can exocytose via exosomes and enter cells as TTR- thyroxine (T4) complex, which consecutively induces the intracellular triiodothyronine (T3) level, followed by T3 secretion out of the cell through the exosomes. The decrease in T3 with the TTR level in 26-week-old mouse muscle, compared to that in 16-week-old muscle, suggests an association of TTR with old muscle. Subsequent studies, including microarray analysis, demonstrated that T3-regulated genes, such as FNDC5 (Fibronectin type III domain containing 5, irisin) and RXRγ (Retinoid X receptor gamma), are influenced by TTR knockdown, implying that thyroid hormones and TTR coordinate with each other with respect to muscle growth and development. These results suggest that, in addition to utilizing T4, skeletal muscle also distributes generated T3 to other tissues and has a vital role in sensing the intracellular T4 level. Furthermore, the results of TTR function with T4 in differentiation will be highly useful in the strategic development of novel therapeutics related to muscle homeostasis and regeneration. View Full-Text
Keywords: muscle satellite cell; transthyretin; thyroid hormone; myogenesis; exosomes; skeletal muscle muscle satellite cell; transthyretin; thyroid hormone; myogenesis; exosomes; skeletal muscle
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Lee, E.J.; Shaikh, S.; Choi, D.; Ahmad, K.; Baig, M.H.; Lim, J.H.; Lee, Y.-H.; Park, S.J.; Kim, Y.-W.; Park, S.-Y.; Choi, I. Transthyretin Maintains Muscle Homeostasis through the Novel Shuttle Pathway of Thyroid Hormones during Myoblast Differentiation. Cells 2019, 8, 1565.

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