Cargando…
FoxO1–Dio2 signaling axis governs cardiomyocyte thyroid hormone metabolism and hypertrophic growth
Forkhead box O (FoxO) proteins and thyroid hormone (TH) have well established roles in cardiovascular morphogenesis and remodeling. However, specific role(s) of individual FoxO family members in stress-induced growth and remodeling of cardiomyocytes remains unknown. Here, we report that FoxO1, but n...
Autores principales: | , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7242347/ https://www.ncbi.nlm.nih.gov/pubmed/32439985 http://dx.doi.org/10.1038/s41467-020-16345-y |
_version_ | 1783537220652630016 |
---|---|
author | Ferdous, Anwarul Wang, Zhao V. Luo, Yuxuan Li, Dan L. Luo, Xiang Schiattarella, Gabriele G. Altamirano, Francisco May, Herman I. Battiprolu, Pavan K. Nguyen, Annie Rothermel, Beverly A. Lavandero, Sergio Gillette, Thomas G. Hill, Joseph A. |
author_facet | Ferdous, Anwarul Wang, Zhao V. Luo, Yuxuan Li, Dan L. Luo, Xiang Schiattarella, Gabriele G. Altamirano, Francisco May, Herman I. Battiprolu, Pavan K. Nguyen, Annie Rothermel, Beverly A. Lavandero, Sergio Gillette, Thomas G. Hill, Joseph A. |
author_sort | Ferdous, Anwarul |
collection | PubMed |
description | Forkhead box O (FoxO) proteins and thyroid hormone (TH) have well established roles in cardiovascular morphogenesis and remodeling. However, specific role(s) of individual FoxO family members in stress-induced growth and remodeling of cardiomyocytes remains unknown. Here, we report that FoxO1, but not FoxO3, activity is essential for reciprocal regulation of types II and III iodothyronine deiodinases (Dio2 and Dio3, respectively), key enzymes involved in intracellular TH metabolism. We further show that Dio2 is a direct transcriptional target of FoxO1, and the FoxO1–Dio2 axis governs TH-induced hypertrophic growth of neonatal cardiomyocytes in vitro and in vivo. Utilizing transverse aortic constriction as a model of hemodynamic stress in wild-type and cardiomyocyte-restricted FoxO1 knockout mice, we unveil an essential role for the FoxO1–Dio2 axis in afterload-induced pathological cardiac remodeling and activation of TRα1. These findings demonstrate a previously unrecognized FoxO1–Dio2 signaling axis in stress-induced cardiomyocyte growth and remodeling and intracellular TH homeostasis. |
format | Online Article Text |
id | pubmed-7242347 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-72423472020-05-29 FoxO1–Dio2 signaling axis governs cardiomyocyte thyroid hormone metabolism and hypertrophic growth Ferdous, Anwarul Wang, Zhao V. Luo, Yuxuan Li, Dan L. Luo, Xiang Schiattarella, Gabriele G. Altamirano, Francisco May, Herman I. Battiprolu, Pavan K. Nguyen, Annie Rothermel, Beverly A. Lavandero, Sergio Gillette, Thomas G. Hill, Joseph A. Nat Commun Article Forkhead box O (FoxO) proteins and thyroid hormone (TH) have well established roles in cardiovascular morphogenesis and remodeling. However, specific role(s) of individual FoxO family members in stress-induced growth and remodeling of cardiomyocytes remains unknown. Here, we report that FoxO1, but not FoxO3, activity is essential for reciprocal regulation of types II and III iodothyronine deiodinases (Dio2 and Dio3, respectively), key enzymes involved in intracellular TH metabolism. We further show that Dio2 is a direct transcriptional target of FoxO1, and the FoxO1–Dio2 axis governs TH-induced hypertrophic growth of neonatal cardiomyocytes in vitro and in vivo. Utilizing transverse aortic constriction as a model of hemodynamic stress in wild-type and cardiomyocyte-restricted FoxO1 knockout mice, we unveil an essential role for the FoxO1–Dio2 axis in afterload-induced pathological cardiac remodeling and activation of TRα1. These findings demonstrate a previously unrecognized FoxO1–Dio2 signaling axis in stress-induced cardiomyocyte growth and remodeling and intracellular TH homeostasis. Nature Publishing Group UK 2020-05-21 /pmc/articles/PMC7242347/ /pubmed/32439985 http://dx.doi.org/10.1038/s41467-020-16345-y Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Ferdous, Anwarul Wang, Zhao V. Luo, Yuxuan Li, Dan L. Luo, Xiang Schiattarella, Gabriele G. Altamirano, Francisco May, Herman I. Battiprolu, Pavan K. Nguyen, Annie Rothermel, Beverly A. Lavandero, Sergio Gillette, Thomas G. Hill, Joseph A. FoxO1–Dio2 signaling axis governs cardiomyocyte thyroid hormone metabolism and hypertrophic growth |
title | FoxO1–Dio2 signaling axis governs cardiomyocyte thyroid hormone metabolism and hypertrophic growth |
title_full | FoxO1–Dio2 signaling axis governs cardiomyocyte thyroid hormone metabolism and hypertrophic growth |
title_fullStr | FoxO1–Dio2 signaling axis governs cardiomyocyte thyroid hormone metabolism and hypertrophic growth |
title_full_unstemmed | FoxO1–Dio2 signaling axis governs cardiomyocyte thyroid hormone metabolism and hypertrophic growth |
title_short | FoxO1–Dio2 signaling axis governs cardiomyocyte thyroid hormone metabolism and hypertrophic growth |
title_sort | foxo1–dio2 signaling axis governs cardiomyocyte thyroid hormone metabolism and hypertrophic growth |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7242347/ https://www.ncbi.nlm.nih.gov/pubmed/32439985 http://dx.doi.org/10.1038/s41467-020-16345-y |
work_keys_str_mv | AT ferdousanwarul foxo1dio2signalingaxisgovernscardiomyocytethyroidhormonemetabolismandhypertrophicgrowth AT wangzhaov foxo1dio2signalingaxisgovernscardiomyocytethyroidhormonemetabolismandhypertrophicgrowth AT luoyuxuan foxo1dio2signalingaxisgovernscardiomyocytethyroidhormonemetabolismandhypertrophicgrowth AT lidanl foxo1dio2signalingaxisgovernscardiomyocytethyroidhormonemetabolismandhypertrophicgrowth AT luoxiang foxo1dio2signalingaxisgovernscardiomyocytethyroidhormonemetabolismandhypertrophicgrowth AT schiattarellagabrieleg foxo1dio2signalingaxisgovernscardiomyocytethyroidhormonemetabolismandhypertrophicgrowth AT altamiranofrancisco foxo1dio2signalingaxisgovernscardiomyocytethyroidhormonemetabolismandhypertrophicgrowth AT mayhermani foxo1dio2signalingaxisgovernscardiomyocytethyroidhormonemetabolismandhypertrophicgrowth AT battiprolupavank foxo1dio2signalingaxisgovernscardiomyocytethyroidhormonemetabolismandhypertrophicgrowth AT nguyenannie foxo1dio2signalingaxisgovernscardiomyocytethyroidhormonemetabolismandhypertrophicgrowth AT rothermelbeverlya foxo1dio2signalingaxisgovernscardiomyocytethyroidhormonemetabolismandhypertrophicgrowth AT lavanderosergio foxo1dio2signalingaxisgovernscardiomyocytethyroidhormonemetabolismandhypertrophicgrowth AT gillettethomasg foxo1dio2signalingaxisgovernscardiomyocytethyroidhormonemetabolismandhypertrophicgrowth AT hilljosepha foxo1dio2signalingaxisgovernscardiomyocytethyroidhormonemetabolismandhypertrophicgrowth |