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MG53 suppresses NF-κB activation to mitigate age-related heart failure

Aging is associated with chronic oxidative stress and inflammation that affect tissue repair and regeneration capacity. MG53 is a TRIM family protein that facilitates repair of cell membrane injury in a redox-dependent manner. Here, we demonstrate that the expression of MG53 was reduced in failing h...

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Autores principales: Wang, Xiaoliang, Li, Xiuchun, Ong, Hannah, Tan, Tao, Park, Ki Ho, Bian, Zehua, Zou, Xunchang, Haggard, Erin, Janssen, Paul M., Merritt, Robert E., Pawlik, Timothy M., Whitson, Bryan A., Mokadam, Nahush A., Cao, Lei, Zhu, Hua, Cai, Chuanxi, Ma, Jianjie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Clinical Investigation 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8492351/
https://www.ncbi.nlm.nih.gov/pubmed/34292883
http://dx.doi.org/10.1172/jci.insight.148375
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author Wang, Xiaoliang
Li, Xiuchun
Ong, Hannah
Tan, Tao
Park, Ki Ho
Bian, Zehua
Zou, Xunchang
Haggard, Erin
Janssen, Paul M.
Merritt, Robert E.
Pawlik, Timothy M.
Whitson, Bryan A.
Mokadam, Nahush A.
Cao, Lei
Zhu, Hua
Cai, Chuanxi
Ma, Jianjie
author_facet Wang, Xiaoliang
Li, Xiuchun
Ong, Hannah
Tan, Tao
Park, Ki Ho
Bian, Zehua
Zou, Xunchang
Haggard, Erin
Janssen, Paul M.
Merritt, Robert E.
Pawlik, Timothy M.
Whitson, Bryan A.
Mokadam, Nahush A.
Cao, Lei
Zhu, Hua
Cai, Chuanxi
Ma, Jianjie
author_sort Wang, Xiaoliang
collection PubMed
description Aging is associated with chronic oxidative stress and inflammation that affect tissue repair and regeneration capacity. MG53 is a TRIM family protein that facilitates repair of cell membrane injury in a redox-dependent manner. Here, we demonstrate that the expression of MG53 was reduced in failing human hearts and aged mouse hearts, concomitant with elevated NF-κB activation. We evaluated the safety and efficacy of longitudinal, systemic administration of recombinant human MG53 (rhMG53) protein in aged mice. Echocardiography and pressure-volume loop measurements revealed beneficial effects of rhMG53 treatment in improving heart function of aged mice. Biochemical and histological studies demonstrated that the cardioprotective effects of rhMG53 are linked to suppression of NF-κB–mediated inflammation, reducing apoptotic cell death and oxidative stress in the aged heart. Repetitive administration of rhMG53 in aged mice did not have adverse effects on major vital organ functions. These findings support the therapeutic value of rhMG53 in treating age-related decline in cardiac function.
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spelling pubmed-84923512021-10-07 MG53 suppresses NF-κB activation to mitigate age-related heart failure Wang, Xiaoliang Li, Xiuchun Ong, Hannah Tan, Tao Park, Ki Ho Bian, Zehua Zou, Xunchang Haggard, Erin Janssen, Paul M. Merritt, Robert E. Pawlik, Timothy M. Whitson, Bryan A. Mokadam, Nahush A. Cao, Lei Zhu, Hua Cai, Chuanxi Ma, Jianjie JCI Insight Research Article Aging is associated with chronic oxidative stress and inflammation that affect tissue repair and regeneration capacity. MG53 is a TRIM family protein that facilitates repair of cell membrane injury in a redox-dependent manner. Here, we demonstrate that the expression of MG53 was reduced in failing human hearts and aged mouse hearts, concomitant with elevated NF-κB activation. We evaluated the safety and efficacy of longitudinal, systemic administration of recombinant human MG53 (rhMG53) protein in aged mice. Echocardiography and pressure-volume loop measurements revealed beneficial effects of rhMG53 treatment in improving heart function of aged mice. Biochemical and histological studies demonstrated that the cardioprotective effects of rhMG53 are linked to suppression of NF-κB–mediated inflammation, reducing apoptotic cell death and oxidative stress in the aged heart. Repetitive administration of rhMG53 in aged mice did not have adverse effects on major vital organ functions. These findings support the therapeutic value of rhMG53 in treating age-related decline in cardiac function. American Society for Clinical Investigation 2021-09-08 /pmc/articles/PMC8492351/ /pubmed/34292883 http://dx.doi.org/10.1172/jci.insight.148375 Text en © 2021 Wang et al. https://creativecommons.org/licenses/by/4.0/This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Wang, Xiaoliang
Li, Xiuchun
Ong, Hannah
Tan, Tao
Park, Ki Ho
Bian, Zehua
Zou, Xunchang
Haggard, Erin
Janssen, Paul M.
Merritt, Robert E.
Pawlik, Timothy M.
Whitson, Bryan A.
Mokadam, Nahush A.
Cao, Lei
Zhu, Hua
Cai, Chuanxi
Ma, Jianjie
MG53 suppresses NF-κB activation to mitigate age-related heart failure
title MG53 suppresses NF-κB activation to mitigate age-related heart failure
title_full MG53 suppresses NF-κB activation to mitigate age-related heart failure
title_fullStr MG53 suppresses NF-κB activation to mitigate age-related heart failure
title_full_unstemmed MG53 suppresses NF-κB activation to mitigate age-related heart failure
title_short MG53 suppresses NF-κB activation to mitigate age-related heart failure
title_sort mg53 suppresses nf-κb activation to mitigate age-related heart failure
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8492351/
https://www.ncbi.nlm.nih.gov/pubmed/34292883
http://dx.doi.org/10.1172/jci.insight.148375
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