ArticleProceedings of the National Academy of Sciences of the United States of America2018
Akt-mediated platelet apoptosis and its therapeutic implications in immune thrombocytopenia.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 72 citations in OpenAlex.
- The glycan fingerprint in immune thrombocytopenia.Research and practice in thrombosis and haemostasis · 2026Article
- Perioperative machine learning models with SHAP interpretation for predicting adverse outcomes in breast cancer surgery.Frontiers in surgery · 2026Article
- Article
- Thrombocytopenia in patients with inborn errors of immunity.BMC immunology · 2025Article
- AHNAK2 confers 5-fluorouracil resistance in colorectal cancer via activation of the AKT/GSK-3β signaling axis.Clinical and experimental medicine · 2025Article
- Iloprost Concentration-Dependently Attenuates Platelet Function and Apoptosis by Elevating PKA Activity.Journal of cellular and molecular medicine · 2025Article
- Aplastic anemia in association with multiple myeloma: clinical and pathophysiological insights.Leukemia & lymphoma · 2024Article
- Desialylation and Apoptosis in Immune Thrombocytopenia: Implications for Pathogenesis and Treatment.Current issues in molecular biology · 2024Review
- Clusterin can mediate apoptosis-induced molecular mechanisms in immune thrombocytopenia.Blood vessels, thrombosis & hemostasis · 2024Article
- Mitofusin-2 Regulates Platelet Mitochondria and Function.Circulation research · 2024Article
- The role of platelet desialylation as a biomarker in primary immune thrombocytopenia: mechanisms and therapeutic perspectives.Frontiers in immunology · 2024Review
- Integration of Transcriptomics and Proteomics Analysis Reveals the Molecular Mechanism ofAntioxidants (Basel, Switzerland) · 2023Article
- Acteoside protects podocyte against apoptosis through regulating AKT/GSK-3β signaling pathway in db/db mice.BMC endocrine disorders · 2023Article
- X-rays Stimulate Granular Secretions and Activate Protein Kinase C Signaling in Human Platelets.Current issues in molecular biology · 2023Article
- How we treat primary immune thrombocytopenia in adults.Journal of hematology & oncology · 2023Review
- Investigation of the Active Compounds and Important Pathways of Huaiqihuang Granule for the Treatment of Immune Thrombocytopenia Using Network Pharmacology and Molecular Docking.BioMed research international · 2023Article
- Platelets promote CRC by activating the C5a/C5aR1 axis via PSGL-1/JNK/STAT1 signaling in tumor-associated macrophages.Theranostics · 2023Article
- Chemically modifiedMolecular therapy. Nucleic acids · 2022Article
- Procoagulant platelet sentinels prevent inflammatory bleeding through GPIIBIIIA and GPVI.Blood · 2022Article
- Beyond Hemostasis: Platelet Innate Immune Interactions and Thromboinflammation.International journal of molecular sciences · 2022Review
Corrections and comments
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Authors and funding
21 authors at 2 institutions in 2 countries.
Funding
Abstract
Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by low platelet count which can cause fatal hemorrhage. ITP patients with antiplatelet glycoprotein (GP) Ib-IX autoantibodies appear refractory to conventional treatments, and the mechanism remains elusive. Here we show that the platelets undergo apoptosis in ITP patients with anti-GPIbα autoantibodies. Consistent with these findings, the anti-GPIbα monoclonal antibodies AN51 and SZ2 induce platelet apoptosis in vitro. We demonstrate that anti-GPIbα antibody binding activates Akt, which elicits platelet apoptosis through activation of phosphodiesterase (PDE3A) and PDE3A-mediated PKA inhibition. Genetic ablation or chemical inhibition of Akt or blocking of Akt signaling abolishes anti-GPIbα antibody-induced platelet apoptosis. We further demonstrate that the antibody-bound platelets are removed in vivo through an apoptosis-dependent manner. Phosphatidylserine (PS) exposure on apoptotic platelets results in phagocytosis of platelets by macrophages in the liver. Notably, inhibition or genetic ablation of Akt or Akt-regulated apoptotic signaling or blockage of PS exposure protects the platelets from clearance. Therefore, our findings reveal pathogenic mechanisms of ITP with anti-GPIbα autoantibodies and, more importantly, suggest therapeutic strategies for thrombocytopenia caused by autoantibodies or other pathogenic factors.
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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.