{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T05:38:58Z","timestamp":1780637938654,"version":"3.54.1"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,8,4]],"date-time":"2022-08-04T00:00:00Z","timestamp":1659571200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Physiol."],"abstract":"<jats:p>Dilated cardiomyopathy (DCM) can lead to heart expansion and severe heart failure, but its specific pathogenesis is still elusive. In many cardiovascular diseases, I-\u03baB kinase-\u03b5 (IKK\u03b5) has been recognized as a pro-inflammatory molecule. In this study, wild-type mice (WT, <jats:italic>n<\/jats:italic> = 14) and IKK\u03b5 knockout mice (IKK\u03b5-KO, <jats:italic>n<\/jats:italic> = 14) were intraperitoneally injected with a cumulative dose of 25\u00a0mg\/kg with Dox or Saline five times in 30\u00a0days. Finally, the experimental mice were divided into WT + Saline group\u3001WT + DOX group\u3001IKK\u03b5-KO + Saline group and IKK\u03b5-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, IKK\u03b5-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 IKK\u03b5-KO mice, and the expression of cardiac gap junction proteins was much higher in IKK\u03b5-KO mice. Further testing found that pyroptosis and apoptosis in the myocardium were also ameliorated in IKK\u03b5-KO mice compared to WT mice after Dox was injected. Mechanistically, our results showed that deficiency of IKK\u03b5 might inhibit the phosphorylation of I\u03baB\u03b1, p65, RelB, and p100 in mouse heart tissues after Dox stimulation. In summary, our research suggests that IKK\u03b5 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.<\/jats:p>","DOI":"10.3389\/fphys.2022.934899","type":"journal-article","created":{"date-parts":[[2022,8,4]],"date-time":"2022-08-04T05:21:22Z","timestamp":1659590482000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["I-\u03baB kinase-\u03b5 deficiency improves doxorubicin-induced dilated cardiomyopathy by inhibiting the NF-\u03baB pathway"],"prefix":"10.3389","volume":"13","author":[{"given":"Yafeng","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yueyue","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiwei","family":"Yao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yide","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ganyi","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuchen","family":"Cai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhibing","family":"Qiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,8,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1111\/j.1600-065X.2012.01095.x","article-title":"Regulation of cell death and autophagy by IKK and NF-\u03baB- critical. mechanisms in immune function and cancer","volume":"246","author":"Baldwin","year":"2012","journal-title":"Immunol. 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