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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...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Clinical Investigation
2021
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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. |
format | Online Article Text |
id | pubmed-8492351 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | American Society for Clinical Investigation |
record_format | MEDLINE/PubMed |
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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