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Thyroid Hormone Transporters MCT8 and OATP1C1 Control Skeletal Muscle Regeneration.

Abstract：

: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.

journal_name

Stem Cell Reports

journal_title

Stem cell reports

authors

Mayerl S,Schmidt M,Doycheva D,Darras VM,Hüttner SS,Boelen A,Visser TJ,Kaether C,Heuer H,von Maltzahn J

doi

10.1016/j.stemcr.2018.03.021

subject

Has Abstract

pub_date

2018-06-05 00:00:00

pages

1959-1974

issue

6

issn

2213-6711

pii

S2213-6711(18)30148-6

journal_volume

10

pub_type

杂志文章

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