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• W1723573887 endingPage "1084" @default.
• W1723573887 startingPage "1076" @default.
• W1723573887 abstract "The cytokine TNF-α, typically considered to have deleterious effects on the heart, can also have cardioprotective effects by inducing formation of a keratin cytoskeletal network in cardiomyocytes. Tumor necrosis factor-α (TNF-α), one of the major stress-induced proinflammatory cytokines, is upregulated in the heart after tissue injury1,2, and its sustained expression can contribute to the development of heart failure1,3,4. Whether TNF-α also exerts cytoprotective effects in heart failure is not known. Here we provide evidence for a cardioprotective function of TNF-α in a genetic heart failure model, desmin-deficient mice. The cardioprotective effects of TNF-α are a consequence of nuclear factor-κB (NF-κB)-mediated ectopic expression in cardiomyocytes of keratin 8 (K8) and keratin 18 (K18), two epithelial-specific intermediate filament proteins5,6. In cardiomyocytes, K8 and K18 (K8/K18) formed an alternative cytoskeletal network that localized mainly at intercalated discs (IDs) and conferred cardioprotection by maintaining normal ID structure and mitochondrial integrity and function. Ectopic induction of K8/K18 expression in cardiomyocytes also occurred in other genetic and experimental models of heart failure. Loss of the K8/K18 network resulted in a maladaptive cardiac phenotype following transverse aortic constriction. In human failing myocardium, where TNF-α expression is upregulated2, K8/K18 were also ectopically expressed and localized primarily at IDs, which did not contain detectable amounts of desmin. Thus, TNF-α– and NF-κB-mediated formation of an alternative, stress-induced intermediate filament cytoskeleton has cardioprotective function in mice and potentially in humans." @default.
• W1723573887 created "2016-06-24" @default.
• W1723573887 creator A5037935879 @default.
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• W1723573887 creator A5088872079 @default.
• W1723573887 creator A5089995475 @default.
• W1723573887 date "2015-08-17" @default.
• W1723573887 modified "2023-10-09" @default.
• W1723573887 title "Tumor necrosis factor-α confers cardioprotection through ectopic expression of keratins K8 and K18" @default.
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• W1723573887 doi "https://doi.org/10.1038/nm.3925" @default.
• W1723573887 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5419049" @default.
• W1723573887 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/26280121" @default.
• W1723573887 hasPublicationYear "2015" @default.
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