ArticleSignal transduction and targeted therapy2021
M2 macrophages, but not M1 macrophages, support megakaryopoiesis by upregulating PI3K-AKT pathway activity.
Article in Signal transduction and targeted therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 67 papers.
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Who cites it
67 citing papers in PubMed, 101 citations in OpenAlex.
- Low-dose oral nicotinamide mononucleotide for immune thrombocytopenia: a phase 1/2 trial.Nature medicine · 2026Trial
- Prophylactic NAC promoted hematopoietic reconstitution by improving endothelial cells after haploidentical HSCT: a phase 3, open-label randomized trial.BMC medicine · 2022Trial
- Unveiling the role of circulating monocyte-macrophage polarization state and PD-L1/PD-L2 expression in newly diagnosed pediatric ITP.Blood research · 2026Article
- Chemotherapy-induced thrombocytopenia: from "platelet counting" to ecological repair of the bone marrow.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2026Review
- Unified bilayer membranes with mechanically reinforced interface for stage-adaptive bone regeneration.Nature communications · 2026Article
- The role ofBlood science (Baltimore, Md.) · 2026Article
- Myeloid Malignancies Beyond the Cell: Targeting the Tumour Microenvironment with Next-Generation Immunotherapies.Cancers · 2026Review
- EBF3 suppresses lung adenocarcinoma progression and immune evasion via transcriptional repression of CCL24.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- Optimizing the Method for Differentiation of Functional Platelets from Human Induced Pluripotent Stem Cells.Stem cell reviews and reports · 2026Article
- Plant-derived extracellular vesicles as tools and targets for inflammatory diseases.Journal of nanobiotechnology · 2026Review
- LMO1 expression in neuroblastoma cells reprograms tumor-associated macrophages to promote metastasis.iScience · 2026Article
- The PI3K-AKT pathway mediates the imbalance of bone marrow macrophage polarization in patients with immune thrombocytopenia.Journal of translational medicine · 2026Article
- PRMT6 is required for initiating and amplifying macrophage-induced inflammation in heterotopic ossification by increasing CCL2 expression.Bone research · 2026Article
- Glycoside Compounds from Blood-Nourishing Chinese Medicinal Herbs: Structural Characteristics, Pharmacological Mechanisms, and Therapeutic Potential for Thrombocytopenia.Molecules (Basel, Switzerland) · 2026Review
- Article
- Macrophages in post-chemoradiotherapy hematopoietic injury: a double-edged sword.Cell communication and signaling : CCS · 2026Review
- Stratified assessment of platelets in sepsis: from dynamic counts to functional phenotypes.Frontiers in immunology · 2026Review
- Eccentric treadmill training and skeletal muscle immunometabolic responses in HFD-induced insulin resistance.Frontiers in immunology · 2026Article
- Piezo1 Upregulation in Monocyte-Derived Macrophages Impairs Post-Myocardial Infarction Cardiac Repair via Defective Efferocytosis and Enhanced Ferroptosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- PDK4 Regulates Inflammatory Injury in Acute-on-chronic Liver Failure by Phosphorylating STAT1-mediated M1 Polarization of Macrophages.Journal of clinical and translational hepatology · 2025Article
7 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
12 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Dysfunctional megakaryopoiesis hampers platelet production, which is closely associated with thrombocytopenia (PT). Macrophages (MФs) are crucial cellular components in the bone marrow (BM) microenvironment. However, the specific effects of M1 MФs or M2 MФs on regulating megakaryocytes (MKs) are largely unknown. In the current study, aberrant BM-M1/M2 MФ polarization, characterized by increased M1 MФs and decreased M2 MФs and accompanied by impaired megakaryopoiesis-supporting abilities, was found in patients with PT post-allotransplant. RNA-seq and western blot analysis showed that the PI3K-AKT pathway was downregulated in the BM MФs of PT patients. Moreover, in vitro treatment with PI3K-AKT activators restored the impaired megakaryopoiesis-supporting ability of MФs from PT patients. Furthermore, we found M1 MФs suppress, whereas M2 MФs support MK maturation and platelet formation in humans. Chemical inhibition of PI3K-AKT pathway reduced megakaryopoiesis-supporting ability of M2 MФs, as indicated by decreased MK count, colony-forming unit number, high-ploidy distribution, and platelet count. Importantly, genetic knockdown of the PI3K-AKT pathway impaired the megakaryopoiesis-supporting ability of MФs both in vitro and in a MФ-specific PI3K-knockdown murine model, indicating a critical role of PI3K-AKT pathway in regulating the megakaryopoiesis-supporting ability of M2 MФs. Furthermore, our preliminary data indicated that TGF-β released by M2 MФs may facilitate megakaryopoiesis through upregulation of the JAK2/STAT5 and MAPK/ERK pathways in MKs. Taken together, our data reveal that M1 and M2 MФs have opposing effects on MKs in a PI3K-AKT pathway-dependent manner, which may lead to new insights into the pathogenesis of thrombocytopenia and provide a potential therapeutic strategy to promote megakaryopoiesis.
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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.