ArticleCells2025
Exogenous Ubiquitin Differentially Modulates the Phenotype and Function of M1 and M2 Macrophages.
Article in Cells, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Biomechanical signaling of cytoskeleton and membrane reorganization in tumor immune chemotactic migration.Theranostics · 2026Review
- The role of the bidirectional regulatory network between immune cells and stromal cells in cardiac repair and fibrosis following myocardial infarction.Frontiers in immunology · 2026Review
- Integrated analysis of cell-in-cell related genes and immune microenvironment in heart failure.Frontiers in cell and developmental biology · 2026Article
- Efferocytosis in heart failure: Mechanisms, dysregulation and therapeutic potential.Theranostics · 2026Review
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Authors and funding
7 authors.
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Abstract
backgroundUnresolved inflammation is a major predictor of heart failure following myocardial infarction. Exogenous ubiquitin (eUB) is shown to decrease inflammatory response and confer cardioprotection in mice 3 days post-ischemia/reperfusion (I/R) injury. Here, we hypothesized that eUB differentially modulates the phenotype and function of M1 and M2 macrophages. METHODS AND
resultsPeritoneal macrophages, pretreated with UB for 30 min, were exposed to IFN-γ (M1 polarization) or IL-4 (M2 polarization) for 72 h. Cytokine/chemokine levels were measured in conditioned media, while cells were used for functional and biochemical assays. eUB reduced TNF-α secretion in M1, and TNF-α and IL-10 secretion in M2 macrophages. eUB induced cytoskeletal reorganization and reduced surface area in M1 macrophages. eUB enhanced M1 migration; however, it decreased M2 macrophage migration and efferocytosis. It decreased STAT1 and FAK phosphorylation in M1, while increasing STAT6 and FAK phosphorylation in M2 macrophages. Total protein ubiquitination remained unchanged. In non-activated macrophages, eUB altered morphology, suppressed IL-1β, IL-2, and IL-5 secretion, and enhanced efferocytosis.
conclusioneUB modulates macrophage polarization, reduces pro-inflammatory cytokine secretion, and alters functional parameters and intracellular signaling. These effects may contribute to the cardioprotective potential of eUB 3 days post-I/R injury.
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