ArticleCell death and differentiation2015
Polycomb-mediated loss of microRNA let-7c determines inflammatory macrophage polarization via PAK1-dependent NF-κB pathway.
Article in Cell death and differentiation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 78 citations in OpenAlex.
- SIRT5-RAC2 Axis Drives Monocyte-to-Macrophage Differentiation to Promote Inflammatory Injury in Premature Ovarian Insufficiency.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- An unexpected tumor-resistant phenotype from floxing PAK1 in a mouse model of colitis associated cancer.Scientific reports · 2025Article
- Review
- Effects of cage vs. net-floor mixed rearing system on goose spleen histomorphology and gene expression profiles.Frontiers in veterinary science · 2024Article
- Macrophage polarization in spinal cord injury repair and the possible role of microRNAs: A review.Heliyon · 2023Review
- Review
- The macrophage polarization by miRNAs and its potential role in the treatment of tumor and inflammation (Review).Oncology reports · 2023Review
- The role of extracellular vesicle-derived miRNAs in adipose tissue function and metabolic health.Immunometabolism (Cobham, Surrey) · 2023Review
- Review
- MicroRNAs in kidney injury and disease.Nature reviews. Nephrology · 2022Review
- Characterization of the microRNA transcriptomes and proteomics of cochlear tissue-derived small extracellular vesicles from mice of different ages after birth.Cellular and molecular life sciences : CMLS · 2022Article
- The Role of miRNA in Regulating the Fate of Monocytes in Health and Cancer.Biomolecules · 2022Review
- EZH2 Inhibitors Suppress Colorectal Cancer by Regulating Macrophage Polarization in the Tumor Microenvironment.Frontiers in immunology · 2022Article
- Ubiquitinated ligation protein NEDD4L participates in MiR-30a-5p attenuated atherosclerosis by regulating macrophage polarization and lipid metabolism.Molecular therapy. Nucleic acids · 2021Article
- MicroRNA: Could It Play a Role in Bovine Endometritis?Inflammation · 2021Review
- Inhibition of EZH2 prevents acute respiratory distress syndrome (ARDS)-associated pulmonary fibrosis by regulating the macrophage polarization phenotype.Respiratory research · 2021Article
- Mesenchymal Stem Cell-Derived Exosomes Induced by IL-1β Attenuate Urethral Stricture Through Let-7c/PAK1/NF-κB-Regulated Macrophage M2 Polarization.Journal of inflammation research · 2021Article
- P21 activated kinase-1 (PAK1) in macrophages is required for promotion of Th17 cell response during helminth infection.Journal of cellular and molecular medicine · 2020Article
- Pak1 maintains epidermal stem cells by regulating Langerhans cells and is required for skin carcinogenesis.Oncogene · 2020Article
- Diversity, Mechanisms, and Significance of Macrophage Plasticity.Annual review of pathology · 2020Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Serine/threonine kinase family members p21-activated kinases (PAKs) are important regulators of cytoskeletal remodeling and cell motility in mononuclear phagocytic system, but their role in macrophage differentiation and polarization remains obscure. We have shown here that inflammatory stimuli induced PAK1 overexpression in human and murine macrophages. Elevated expression of PAK1 contributed to macrophage M1 polarization and lipopolysaccharide (LPS)-induced endotoxin shock. We further observed that epigenetic loss of microRNA let-7c due to enhancer of zeste homolog 2 (EZH2) upregulation determined PAK1 elevation and inflammatory phenotype in M1 macrophages. EZH2/let-7c/PAK1 axis promotes macrophage M1 polarization via NIK-IKK-NF-κB signaling. Moreover, pharmacological and genetic ablation with EZH2/let-7c/PAK1 axis blunted inflammatory phenotype in M1 macrophages. Critically, either myeloid-restricted PAK1 deletion (PAK1(Lyz2cre)) or pharmacological and genetic ablation with EZH2/let-7c/PAK1 signal resulted in resistance to LPS-induced endotoxin shock via blunting macrophage M1 polarization. PAK1, therefore, is an essential controller of inflammatory macrophage polarization, regulating immune responses against pathogenic stimuli.
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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.