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Beta‐arrestin 2 mediates cardiac hypertrophy induced by thyroid hormones via AT1R
Author(s) -
Lino Caroline Antunes,
Bortoli Teixeira Larissa,
Capelupe Simões Sarah,
Oliveira Silva Tábatha,
Diniz Gabriela Placoná,
CostaNeto Claudio Miguel,
BarretoChaves Maria Luiza Morais
Publication year - 2021
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.30187
Subject(s) - signal transduction , angiotensin ii , microbiology and biotechnology , receptor , biology , muscle hypertrophy , endocrinology , medicine , stimulation , mapk/erk pathway , pharmacology
We have previously reported that angiotensin II receptor type 1 (AT1R) contributes to the hypertrophic effects of thyroid hormones (TH) in cardiac cells. Even though evidence indicates crosstalks between TH and AT1R, the underlying mechanisms are poorly understood. Beta‐arrestin (ARRB) signaling has been described as noncanonical signal transduction pathway that exerts important effects in the cardiovascular system through G‐protein‐coupled receptors, as AT1R. Herein, we investigated the contribution of ARRB signaling in TH‐induced cardiomyocyte hypertrophy. Primary cardiomyocyte cultures were treated with Triiodothyronine (T3) to induce cell hypertrophy. T3 rapidly activates extracellular signal‐regulated kinase 1/2 (ERK1/2) signaling, which was partially inhibited by AT1R blockade. Also, ERK1/2 inhibition attenuated the hypertrophic effects of T3. ARRB2 was upregulated by T3, and small interfering RNA assays revealed the role of ARRB2—but not ARRB1—on ERK1/2 activation and cardiomyocyte hypertrophy. Corroborating these findings, the ARRB2‐overexpressed cells showed increased expression of hypertrophic markers, which were attenuated by ERK1/2 inhibition. Immunocytochemistry and immunoprecipitation assays revealed the increased expression of nuclear AT1R after T3 stimulation and the increased interaction of AT1R/ARRB2. The inhibition of endocytosis also attenuated the T3 effects on cardiac cells. Our results evidence the contribution of ARRB2 on ERK1/2 activation and cardiomyocyte hypertrophy induced by T3 via AT1R.