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MicroRNA 21 Is a Homeostatic Regulator of Macrophage Polarization and Prevents Prostaglandin E2-Mediated M2 Generation
Open accessAbstract
Macrophages dictate both initiation and resolution of inflammation. During acute inflammation classically activated macrophages (M1) predominate, and during the resolution phase alternative macrophages (M2) are dominant. The molecular mechanisms involved in macrophage polarization are understudied. MicroRNAs are differentially expressed in M1 and M2 macrophages that influence macrophage polarization. We identified a role of miR-21 in macrophage polarization, and found that cross-talk between miR-21 and the lipid mediator prostaglandin E2 (PGE2) is a determining factor in macrophage polarization. miR-21 inhibition impairs expression of M2 signature genes but not M1 genes. PGE2 and its downstream effectors PKA and Epac inhibit miR-21 expression and enhance expression of M2 genes, and this effect is more pronounced in miR-21-/- cells. Among potential targets involved in macrophage polarization, we found that STAT3 and SOCS1 were enhanced in miR-21-/- cells and further enhanced by PGE2. We found that STAT3 was a direct target of miR-21 in macrophages. Silencing the STAT3 gene abolished PGE2-mediated expression of M2 genes in miR-21-/- macrophages. These data shed light on the molecular brakes involved in homeostatic macrophage polarization and suggest new therapeutic strategies to prevent inflammatory responses.
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“The pro-inflammatory phenotype is also induced by prostaglandin E2 (PGE2) which inhibits miR-21a, responsible for regulation STAT3, thus preventing the switch from M1 to M2 macrophages [118].”
From MicroRNAs as Regulators of Phagocytosis (2022) · cites this paper as [118]
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Metadata
- Authors
- Wang, Z., Brandt, S., Medeiros, A., Wang, S., Wu, H., Dent, A., & Serezani, C. H.
- Affiliations
- Indiana University School of Medicine (US)
- Corresponding author
- Serezani, C. Henrique
- Venue
- PLOS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2015-02-23
- Volume
- 10
- Issue
- 2
- Pages
- e0115855
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC4338261
- OpenAlex
- W2015054805
- Cited by
- 169
- References
- 58
- Citations by year
- 2026: 7 · 2025: 9 · 2024: 12 · 2023: 6 · 2022: 22 · 2021: 23 · 2020: 18 · 2019: 17 · 2018: 14 · 2017: 15 · 2016: 9 · 2015: 3
- FWCI
- 6.74
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Acervo Digital da Universidade Estadual Paulista (Universidade Estadual Paulista) (submittedVersion, other-oa)
- Americanae (AECID Library) (submittedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, other-oa)
- IUScholarWorks (Indiana University) (submittedVersion)
- PMC
- Funders
- Ralph W. and Grace M. Showalter Research Trust Fund
- National Institutes of Health (HL-103777-01, HL-124159-01, HL-103777)
- National Heart, Lung, and Blood Institute (HL-124159-01, HL10377701, K99HL103777, R01HL124159, R00HL103777)
- National Institute of Allergy and Infectious Diseases (R21AI079349, T32AI060519)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Immunology and Microbiology › Immunology › Macrophage Migration Inhibitory Factor
- Keywords
- miR-21, macrophage polarization, M2 macrophages, prostaglandin E2, STAT3, SOCS1, protein kinase A, Epac, inflammation resolution, microRNA regulation, M1 macrophages
- MeSH terms
- Suppressor of Cytokine Signaling 1 Protein, Acetylcysteine, Animals, Erythromycin, Female, Homeostasis, Macrophage Activation, Macrophages, Dinoprostone, Cell Polarity, Cyclic AMP-Dependent Protein Kinases, Mice, Knockout, Gene Silencing, MicroRNAs, STAT3 Transcription Factor, Suppressor of Cytokine Signaling Proteins, Mice
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