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Thyroid Hormone Transporters MCT8 and OATP1C1 Control Skeletal Muscle Regeneration
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 re...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5993536/ https://www.ncbi.nlm.nih.gov/pubmed/29706500 http://dx.doi.org/10.1016/j.stemcr.2018.03.021 |
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author | Mayerl, Steffen Schmidt, Manuel Doycheva, Denica Darras, Veerle M. Hüttner, Sören S. Boelen, Anita Visser, Theo J. Kaether, Christoph Heuer, Heike von Maltzahn, Julia |
author_facet | Mayerl, Steffen Schmidt, Manuel Doycheva, Denica Darras, Veerle M. Hüttner, Sören S. Boelen, Anita Visser, Theo J. Kaether, Christoph Heuer, Heike von Maltzahn, Julia |
author_sort | Mayerl, Steffen |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-5993536 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-59935362018-06-11 Thyroid Hormone Transporters MCT8 and OATP1C1 Control Skeletal Muscle Regeneration Mayerl, Steffen Schmidt, Manuel Doycheva, Denica Darras, Veerle M. Hüttner, Sören S. Boelen, Anita Visser, Theo J. Kaether, Christoph Heuer, Heike von Maltzahn, Julia Stem Cell Reports Article 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. Elsevier 2018-04-26 /pmc/articles/PMC5993536/ /pubmed/29706500 http://dx.doi.org/10.1016/j.stemcr.2018.03.021 Text en © 2018 The Author(s) http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Mayerl, Steffen Schmidt, Manuel Doycheva, Denica Darras, Veerle M. Hüttner, Sören S. Boelen, Anita Visser, Theo J. Kaether, Christoph Heuer, Heike von Maltzahn, Julia Thyroid Hormone Transporters MCT8 and OATP1C1 Control Skeletal Muscle Regeneration |
title | Thyroid Hormone Transporters MCT8 and OATP1C1 Control Skeletal Muscle Regeneration |
title_full | Thyroid Hormone Transporters MCT8 and OATP1C1 Control Skeletal Muscle Regeneration |
title_fullStr | Thyroid Hormone Transporters MCT8 and OATP1C1 Control Skeletal Muscle Regeneration |
title_full_unstemmed | Thyroid Hormone Transporters MCT8 and OATP1C1 Control Skeletal Muscle Regeneration |
title_short | Thyroid Hormone Transporters MCT8 and OATP1C1 Control Skeletal Muscle Regeneration |
title_sort | thyroid hormone transporters mct8 and oatp1c1 control skeletal muscle regeneration |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5993536/ https://www.ncbi.nlm.nih.gov/pubmed/29706500 http://dx.doi.org/10.1016/j.stemcr.2018.03.021 |
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