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SOCS3 Negatively Regulates Cardiac Hypertrophy via Targeting GRP78-Mediated ER Stress During Pressure Overload
Pressure overload-induced hypertrophic remodeling is a critical pathological process leading to heart failure (HF). Suppressor of cytokine signaling-3 (SOCS3) has been demonstrated to protect against cardiac hypertrophy and dysfunction, but its mechanisms are largely unknown. Using primary cardiomyo...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7874011/ https://www.ncbi.nlm.nih.gov/pubmed/33585485 http://dx.doi.org/10.3389/fcell.2021.629932 |
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author | Liu, Shuang Sun, Wen-Chang Zhang, Yun-Long Lin, Qiu-Yue Liao, Jia-Wei Song, Gui-Rong Ma, Xiao-Lei Li, Hui-Hua Zhang, Bo |
author_facet | Liu, Shuang Sun, Wen-Chang Zhang, Yun-Long Lin, Qiu-Yue Liao, Jia-Wei Song, Gui-Rong Ma, Xiao-Lei Li, Hui-Hua Zhang, Bo |
author_sort | Liu, Shuang |
collection | PubMed |
description | Pressure overload-induced hypertrophic remodeling is a critical pathological process leading to heart failure (HF). Suppressor of cytokine signaling-3 (SOCS3) has been demonstrated to protect against cardiac hypertrophy and dysfunction, but its mechanisms are largely unknown. Using primary cardiomyocytes and cardiac-specific SOCS3 knockout (SOCS3cko) or overexpression mice, we demonstrated that modulation of SOCS3 level influenced cardiomyocyte hypertrophy, apoptosis and cardiac dysfunction induced by hypertrophic stimuli. We found that glucose regulatory protein 78 (GRP78) was a direct target of SOCS3, and that overexpression of SOCS3 inhibited cardiomyocyte hypertrophy and apoptosis through promoting proteasomal degradation of GRP78, thereby inhibiting activation of endoplasmic reticulum (ER) stress and mitophagy in the heart. Thus, our results uncover SOCS3-GRP78-mediated ER stress as a novel mechanism in the transition from cardiac hypertrophy to HF induced by sustained pressure overload, and suggest that modulating this pathway may provide a new therapeutic approach for hypertrophic heart diseases. |
format | Online Article Text |
id | pubmed-7874011 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-78740112021-02-11 SOCS3 Negatively Regulates Cardiac Hypertrophy via Targeting GRP78-Mediated ER Stress During Pressure Overload Liu, Shuang Sun, Wen-Chang Zhang, Yun-Long Lin, Qiu-Yue Liao, Jia-Wei Song, Gui-Rong Ma, Xiao-Lei Li, Hui-Hua Zhang, Bo Front Cell Dev Biol Cell and Developmental Biology Pressure overload-induced hypertrophic remodeling is a critical pathological process leading to heart failure (HF). Suppressor of cytokine signaling-3 (SOCS3) has been demonstrated to protect against cardiac hypertrophy and dysfunction, but its mechanisms are largely unknown. Using primary cardiomyocytes and cardiac-specific SOCS3 knockout (SOCS3cko) or overexpression mice, we demonstrated that modulation of SOCS3 level influenced cardiomyocyte hypertrophy, apoptosis and cardiac dysfunction induced by hypertrophic stimuli. We found that glucose regulatory protein 78 (GRP78) was a direct target of SOCS3, and that overexpression of SOCS3 inhibited cardiomyocyte hypertrophy and apoptosis through promoting proteasomal degradation of GRP78, thereby inhibiting activation of endoplasmic reticulum (ER) stress and mitophagy in the heart. Thus, our results uncover SOCS3-GRP78-mediated ER stress as a novel mechanism in the transition from cardiac hypertrophy to HF induced by sustained pressure overload, and suggest that modulating this pathway may provide a new therapeutic approach for hypertrophic heart diseases. Frontiers Media S.A. 2021-01-26 /pmc/articles/PMC7874011/ /pubmed/33585485 http://dx.doi.org/10.3389/fcell.2021.629932 Text en Copyright © 2021 Liu, Sun, Zhang, Lin, Liao, Song, Ma, Li and Zhang. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Cell and Developmental Biology Liu, Shuang Sun, Wen-Chang Zhang, Yun-Long Lin, Qiu-Yue Liao, Jia-Wei Song, Gui-Rong Ma, Xiao-Lei Li, Hui-Hua Zhang, Bo SOCS3 Negatively Regulates Cardiac Hypertrophy via Targeting GRP78-Mediated ER Stress During Pressure Overload |
title | SOCS3 Negatively Regulates Cardiac Hypertrophy via Targeting GRP78-Mediated ER Stress During Pressure Overload |
title_full | SOCS3 Negatively Regulates Cardiac Hypertrophy via Targeting GRP78-Mediated ER Stress During Pressure Overload |
title_fullStr | SOCS3 Negatively Regulates Cardiac Hypertrophy via Targeting GRP78-Mediated ER Stress During Pressure Overload |
title_full_unstemmed | SOCS3 Negatively Regulates Cardiac Hypertrophy via Targeting GRP78-Mediated ER Stress During Pressure Overload |
title_short | SOCS3 Negatively Regulates Cardiac Hypertrophy via Targeting GRP78-Mediated ER Stress During Pressure Overload |
title_sort | socs3 negatively regulates cardiac hypertrophy via targeting grp78-mediated er stress during pressure overload |
topic | Cell and Developmental Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7874011/ https://www.ncbi.nlm.nih.gov/pubmed/33585485 http://dx.doi.org/10.3389/fcell.2021.629932 |
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