ArticleCell death discovery2024
CircMETTL3-156aa reshapes the glycolytic metabolism of macrophages to promote M1 polarization and induce cytokine storms in sHLH.
Article in Cell death discovery, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
What it found
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Who cites it
14 citing papers in PubMed.
- HSV-1 metabolic hijacking: Mechanisms to precision therapeutics.Virulence · 2026Review
- CHAC2-mediated glutathione metabolic reprogramming drives N1 polarization of bone marrow neutrophils and exacerbates inflammatory comorbidities.International journal of oral science · 2026Article
- Protein lactylation in health and diseases: molecular mechanisms, biological significance, and clinical implications.Signal transduction and targeted therapy · 2026Review
- Lactylation modification in extracellular vesicles: A key regulator of cellular communication.iScience · 2026Review
- Article
- Advances in understanding exosome-mediated regulation of macrophage function.Frontiers in immunology · 2026Review
- CircMETTL3 Inhibits HJournal of ophthalmology · 2026Article
- Mechanistic Research on the Crosstalk Between Macrophage Polarization and Energy Metabolic Reprogramming in Hepatocellular Carcinoma.Journal of hepatocellular carcinoma · 2026Review
- Lactylation: a novel epigenetic bridge connecting metabolic reprogramming and immune dysregulation in sepsis-associated ARDS.Frontiers in immunology · 2026Review
- Exploring the mechanisms of mutual influence between lactylation and macrophage polarization in the context of disease.Clinical and translational medicine · 2025Review
- Research advances of lactylation modification in breast cancer.Discover oncology · 2025Review
- Lactylation modifications in urological diseases: molecular mechanisms and biological implications.Clinical epigenetics · 2025Review
- Case Report: Longitudinal mass cytometry profiling of a patient with disseminated histoplasmosis and secondary hemophagocytic lymphohistiocytosis.Frontiers in immunology · 2025Article
- dsHMGB1, released from IL-17A-induced pyroptotic prostate epithelial cells, drives M1 polarization by promoting Pfkp-mediated glycolysis via Jak2/Stat1 transcription in experimental autoimmune prostatitis.International journal of biological sciences · 2025Article
Corrections and comments
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Authors and funding
12 authors.
Funding
Abstract
Persistent macrophage activation and cytokine storms are critical causes for the rapid disease progression and high mortality rate of Secondary Hemophagocytic lymphohistiocytosis (sHLH). Identification of key regulatory factors that govern the activation of macrophages is vital. Plasma exosomal circular RNAs (circRNAs) are considered important biomarkers and potential therapeutic targets for various diseases, however, their function in sHLH is still unclear. In this study, we demonstrated for the first time that circMETTL3, derived from METTL3, is upregulated in sHLH patient plasma exosomes, which may plays an important role in the diagnosis of sHLH. Significantly, we also revealed that a novel peptide encoded by circMETTL3, METTL3-156aa, is an inducer of M1 macrophage polarization, which is responsible for the development of cytokine storms during sHLH. We then identified that METTL3-156aa binding with lactate dehydrogenase A (LDHA) and promotes M1 macrophage polarization by enhancing macrophage glycolysis. Additionally, the glycolysis metabolite lactate upregulates the cleavage factor SRSF10 expression by lactylation. This results in increased splicing of the pre-METTL3 mRNA, leading to an enchance in the production of cirMETTL3. Therefore, our results suggest that the circMETTL3/METTL3-156aa/LDHA/Lactate/SRSF10 axis forms a positive feedback loop and may be a novel therapeutic target for the treatment of sHLH.
Identifiers
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.