Cited by 169Immune cells in cancerMicroRNA in disease regulationMacrophage Migration Inhibitory Factor

MicroRNA 21 Is a Homeostatic Regulator of Macrophage Polarization and Prevents Prostaglandin E2-Mediated M2 Generation

Open access
Wang, Zhuo, Brandt, Stephanie, Medeiros, Alexandra, Wang, Soujuan, Wu, Hao, Dent, Alexander, Serezani, C. Henrique·2015·PLOS ONE

Abstract

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.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1371/journal.pone.0115855

Cites

58 of 58 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Prostaglandin E2 inhibits miR-21a, responsible for regulation STAT3, thus preventing the switch from M1 to M2 macrophages.

    “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]

    The Results section (‘miR-21 is an endogenous brake in PGE2-mediated M2 polarization’; page unavailable) reports that PGE2 decreases M1 markers and increases M2 markers. The Discussion confirms that PGE2 inhibits miR-21 expression, but says this enhances—not prevents—M2 polarization. The claim reverses the paper’s central finding. (LLM, conf=0.90)

    Checked by a reasoning model — may be wrong.

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

1 retracted

Flagged first, then by citations

Cited by

Sorted by citations

Authors
Wang, Z., Brandt, S., Medeiros, A., Wang, S., Wu, H., Dent, A., & Serezani, C. H.
Affiliations
  • Indiana University School of Medicine (US)
  • Universidade Estadual Paulista (Unesp) (BR)
Corresponding author
Serezani, C. Henrique
Venue
PLOS ONE
Published
2015-02-23
Volume
10
Issue
2
Pages
e0115855
ISSN
1932-6203 (ISSN-L)
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 · 2014: 1 · 2012: 1
FWCI
6.74
Type
journal article
Language
en
Open access
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

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review