ORIGINAL RESEARCH article
Front. Cell Dev. Biol.
Sec. Epigenomics and Epigenetics
This article is part of the Research TopicHistone Lactylation and Glucose Metabolism: Epigenetic Insights into Tumors and Inflammatory DiseasesView all articles
DANCR promotes septic cardiomyopathy by enhancing macrophage glycolytic reprogramming via the IGF2BP2/HK2 axis
Provisionally accepted
- 1Department of Clinical Laboratory, Affiliated Hospital of Shandong Second Medical University, Weifang, China
- 2School of Medical Laboratory, Shandong Second Medical University, Weifang, China
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Background: Metabolic reprogramming of macrophages shapes their phenotypic plasticity and contributes to the progression of septic cardiomyopathy. This study investigated the role of DANCR in modulating of macrophage glycolysis, thereby elucidating its mechanism for augmenting septic cardiomyopathy. Method: THP-1-derived macrophages were stimulated with LPS and subjected to DANCR knockdown or HK2 overexpression. Inflammatory cytokine levels, M1 polarization, and glycolytic activity were evaluated. Conditioned media from treated macrophages were used to treat cardiomyocytes. Mechanistic analyses, including bioinformatics, RNA immunoprecipitation (RIP), and RNA stability assays, were performed to identify downstream targets of DANCR. Result: DANCR silencing attenuated M1 polarization and activity in macrophages, improved cardiomyocyte viability and reducing apoptosis. Mechanistically, DANCR upregulated HK2 expression by enhancing IGF2BP2-mediated mRNA stabilization. HK2 overexpression reversed the protective effects of DANCR knockdown, whereas pharmacologic inhibition of glycolysis counteracted the effects of HK2 overexpression, confirming the involvement of the DANCR/IGF2BP2/HK2 axis. Conclusion: DANCR promotes septic cardiomyopathy by enhancing macrophage glycolytic reprogramming via the IGF2BP2/HK2 axis. Targeting this pathway may provide a novel therapeutic strategy.
Keywords: Septic cardiomyopathy, DANCR, macrophage M1 polarization, Glycolysis, IGF2BP2, HK2
Received: 15 May 2025; Accepted: 17 Nov 2025.
Copyright: © 2025 Ma, Liu, Zhao, Liu and Zhang. 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) or licensor 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.
* Correspondence: Xuguang Zhang, xug-zhang@ldy.edu.rs
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