Helmholtz Gemeinschaft


FoxO1-Dio2 signaling axis governs cardiomyocyte thyroid hormone metabolism and hypertrophic growth

PDF (Original Article) - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
[img] Other (Supplementary Information)

Item Type:Article
Title:FoxO1-Dio2 signaling axis governs cardiomyocyte thyroid hormone metabolism and hypertrophic growth
Creators Name:Ferdous, A. and Wang, Z.V. and Luo, Y. and Li, D.L. and Luo, X. and Schiattarella, G.G. and Altamirano, F. and May, H.I. and Battiprolu, P.K. and Nguyen, A. and Rothermel, B.A. and Lavandero, S. and Gillette, T.G. and Hill, J.A.
Abstract: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.
Keywords:Cardiomegaly, Cardiac Myocytes, Cultured Cells, Forkhead Box Protein O1, Gene Expression Regulation, Iodide Peroxidase, Knockout Mice, Newborn Animals, Signal Transduction, Thyroid Hormones, Ventricular Remodeling, Animals, Mice, Rats
Source:Nature Communications
Publisher:Nature Publishing Group
Page Range:2551
Date:21 May 2020
Official Publication:https://doi.org/10.1038/s41467-020-16345-y
PubMed:View item in PubMed

Repository Staff Only: item control page


Downloads per month over past year

Open Access
MDC Library