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I-κB kinase-ε deficiency improves doxorubicin-induced dilated cardiomyopathy by inhibiting the NF-κB pathway
Dilated cardiomyopathy (DCM) can lead to heart expansion and severe heart failure, but its specific pathogenesis is still elusive. In many cardiovascular diseases, I-κB kinase-ε (IKKε) has been recognized as a pro-inflammatory molecule. In this study, wild-type mice (WT, n = 14) and IKKε knockout mi...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9386238/ https://www.ncbi.nlm.nih.gov/pubmed/35991177 http://dx.doi.org/10.3389/fphys.2022.934899 |
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author | Liu, Yafeng Xu, Yueyue Yao, Yiwei Cao, Yide Chen, Ganyi Cai, Yuchen Chen, Wen Chen, Xin Qiu, Zhibing |
author_facet | Liu, Yafeng Xu, Yueyue Yao, Yiwei Cao, Yide Chen, Ganyi Cai, Yuchen Chen, Wen Chen, Xin Qiu, Zhibing |
author_sort | Liu, Yafeng |
collection | PubMed |
description | Dilated cardiomyopathy (DCM) can lead to heart expansion and severe heart failure, but its specific pathogenesis is still elusive. In many cardiovascular diseases, I-κB kinase-ε (IKKε) has been recognized as a pro-inflammatory molecule. In this study, wild-type mice (WT, n = 14) and IKKε knockout mice (IKKε-KO, n = 14) were intraperitoneally injected with a cumulative dose of 25 mg/kg with Dox or Saline five times in 30 days. Finally, the experimental mice were divided into WT + Saline group、WT + DOX group、IKKε-KO + Saline group and IKKε-KO + Dox group. Echocardiography was performed to assess cardiac structure and function. Moreover, the mechanism was validated by immunohistochemistry and western blotting. Our results demonstrated that compared to WT + Dox mice, IKKε-KO + Dox mice exhibited attenuation of dilated cardiomyopathy-related morphological changes and alleviation of heart failure. Additionally, compared to the WT mice after Dox-injected, the expression of fibrosis and proinflammatory were decreased in IKKε-KO mice, and the expression of cardiac gap junction proteins was much higher in IKKε-KO mice. Further testing found that pyroptosis and apoptosis in the myocardium were also ameliorated in IKKε-KO mice compared to WT mice after Dox was injected. Mechanistically, our results showed that deficiency of IKKε might inhibit the phosphorylation of IκBα, p65, RelB, and p100 in mouse heart tissues after Dox stimulation. In summary, our research suggests that IKKε might play an essential role in the development of Dox-induced dilated cardiomyopathy and may be a potential target for the treatment of dilated cardiomyopathy in the future. |
format | Online Article Text |
id | pubmed-9386238 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-93862382022-08-19 I-κB kinase-ε deficiency improves doxorubicin-induced dilated cardiomyopathy by inhibiting the NF-κB pathway Liu, Yafeng Xu, Yueyue Yao, Yiwei Cao, Yide Chen, Ganyi Cai, Yuchen Chen, Wen Chen, Xin Qiu, Zhibing Front Physiol Physiology Dilated cardiomyopathy (DCM) can lead to heart expansion and severe heart failure, but its specific pathogenesis is still elusive. In many cardiovascular diseases, I-κB kinase-ε (IKKε) has been recognized as a pro-inflammatory molecule. In this study, wild-type mice (WT, n = 14) and IKKε knockout mice (IKKε-KO, n = 14) were intraperitoneally injected with a cumulative dose of 25 mg/kg with Dox or Saline five times in 30 days. Finally, the experimental mice were divided into WT + Saline group、WT + DOX group、IKKε-KO + Saline group and IKKε-KO + Dox group. Echocardiography was performed to assess cardiac structure and function. Moreover, the mechanism was validated by immunohistochemistry and western blotting. Our results demonstrated that compared to WT + Dox mice, IKKε-KO + Dox mice exhibited attenuation of dilated cardiomyopathy-related morphological changes and alleviation of heart failure. Additionally, compared to the WT mice after Dox-injected, the expression of fibrosis and proinflammatory were decreased in IKKε-KO mice, and the expression of cardiac gap junction proteins was much higher in IKKε-KO mice. Further testing found that pyroptosis and apoptosis in the myocardium were also ameliorated in IKKε-KO mice compared to WT mice after Dox was injected. Mechanistically, our results showed that deficiency of IKKε might inhibit the phosphorylation of IκBα, p65, RelB, and p100 in mouse heart tissues after Dox stimulation. In summary, our research suggests that IKKε might play an essential role in the development of Dox-induced dilated cardiomyopathy and may be a potential target for the treatment of dilated cardiomyopathy in the future. Frontiers Media S.A. 2022-08-04 /pmc/articles/PMC9386238/ /pubmed/35991177 http://dx.doi.org/10.3389/fphys.2022.934899 Text en Copyright © 2022 Liu, Xu, Yao, Cao, Chen, Cai, Chen, Chen and Qiu. https://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 | Physiology Liu, Yafeng Xu, Yueyue Yao, Yiwei Cao, Yide Chen, Ganyi Cai, Yuchen Chen, Wen Chen, Xin Qiu, Zhibing I-κB kinase-ε deficiency improves doxorubicin-induced dilated cardiomyopathy by inhibiting the NF-κB pathway |
title | I-κB kinase-ε deficiency improves doxorubicin-induced dilated cardiomyopathy by inhibiting the NF-κB pathway |
title_full | I-κB kinase-ε deficiency improves doxorubicin-induced dilated cardiomyopathy by inhibiting the NF-κB pathway |
title_fullStr | I-κB kinase-ε deficiency improves doxorubicin-induced dilated cardiomyopathy by inhibiting the NF-κB pathway |
title_full_unstemmed | I-κB kinase-ε deficiency improves doxorubicin-induced dilated cardiomyopathy by inhibiting the NF-κB pathway |
title_short | I-κB kinase-ε deficiency improves doxorubicin-induced dilated cardiomyopathy by inhibiting the NF-κB pathway |
title_sort | i-κb kinase-ε deficiency improves doxorubicin-induced dilated cardiomyopathy by inhibiting the nf-κb pathway |
topic | Physiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9386238/ https://www.ncbi.nlm.nih.gov/pubmed/35991177 http://dx.doi.org/10.3389/fphys.2022.934899 |
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