Volledige artikel als pdf: Thyroid Hormone Signaling in Muscle Development, Repair and Metabolism
Jang-Won Lee1, Nam-Ho Kim1 and Anna Milanesi2*
1Department of Neurosurgery, Cedars-Sinai Medical Center, USA
2Department of Medicine, Division of Endocrinology, VA Greater Los Angeles
Healthcare System, USA
Intracellular Inactivation of Thyroid Hormone Is a Survival Mechanism for Muscle Stem Cell Proliferation and Lineage Progression
Highlights
• •D3 is induced in proliferating satellite cells thereby reducing thyroid signaling
• •D3 depletion causes massive cell apoptosis in vitro and in vivo
• •Apoptosis requires FoxO3, a TH target gene
• •Satellite cells customize TH signature and adapt it to their functional needs
Summary
Precise control of the thyroid hormone (T3)-dependent transcriptional program is required by multiple cell systems, including muscle stem cells.
Deciphering how this is achieved and how the T3 signal is controlled in stem cell niches is essentially unknown.
We report that in response to proliferative stimuli such as acute skeletal muscle injury, type 3 deiodinase (D3), the thyroid hormone-inactivating enzyme, is induced in satellite cells where it reduces intracellular thyroid signaling.
Satellite cell-specific genetic ablation of dio3 severely impairs skeletal muscle regeneration.
This impairment is due to massive satellite cell apoptosis caused by exposure of activated satellite cells to the circulating TH.
The execution of this proapoptotic program requires an intact FoxO3/MyoD axis, both genes positively regulated by intracellular TH.
Thus, D3 is dynamically exploited in vivo to chronically attenuate TH signaling under basal conditions while also being available to acutely increase gene programs required for satellite cell lineage progression.
This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).
Received: August 7, 2014; Received in revised form: September 17, 2014; Accepted: October 8, 2014; Published Online: November 13, 2014
© 2014 The Authors. Published by Elsevier Inc. User rights governed by an Open Access license.
artikel:
http://www.cell.com/cell-metabolism/ful ... 50-4131(14
.