Thyroid Hormone Transporters MCT8 and OATP1C1 Control Skeletal Muscle Regeneration.

Steffen Mayerl, Manuel Schmidt, Denica Doycheva, Veerle M Darras, Sören S Hüttner, Anita Boelen, Theo J Visser, Christoph Kaether, Heike Heuer, Julia von Maltzahn

Stem cell reports 2018 Jun 05

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Thyroid hormone (TH) transporters are required for the transmembrane passage of TH in target cells. In humans, inactivating mutations in the TH transporter MCT8 cause the Allan-Herndon-Dudley syndrome, characterized by severe neuromuscular symptoms and an abnormal TH serum profile, which is fully replicated in Mct8 knockout mice and Mct8/Oatp1c1 double-knockout (M/O DKO) mice. Analysis of tissue TH content and expression of TH-regulated genes indicate a thyrotoxic state in Mct8-deficient skeletal muscles. Both TH transporters are upregulated in activated satellite cells (SCs). In M/O DKO mice, we observed a strongly reduced number of differentiated SCs, suggesting an impaired stem cell function. Moreover, M/O DKO mice and mice lacking both transporters exclusively in SCs showed impaired skeletal muscle regeneration. Our data provide solid evidence for a unique gate-keeper function of MCT8 and OATP1C1 in SC activation, underscoring the importance of a finely tuned TH signaling during myogenesis. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Citation

Steffen Mayerl, Manuel Schmidt, Denica Doycheva, Veerle M Darras, Sören S Hüttner, Anita Boelen, Theo J Visser, Christoph Kaether, Heike Heuer, Julia von Maltzahn. Thyroid Hormone Transporters MCT8 and OATP1C1 Control Skeletal Muscle Regeneration. Stem cell reports. 2018 Jun 05;10(6):1959-1974