ArticleBlood2009
Platelet factor 4 regulates megakaryopoiesis through low-density lipoprotein receptor-related protein 1 (LRP1) on megakaryocytes.
Article in Blood, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
33 citing papers in PubMed, 59 citations in OpenAlex.
- Gut Microbiota Regulates Systemic Inflammatory Response and Compensatory Anti-Inflammatory Response Syndromes by Targeting PF4Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
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- Platelet factor 4 in cognitive, immune and hematopoietic aging: emerging evidence and translational challenges.Frontiers in immunology · 2026Review
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- Understanding and reversing mammary tumor-driven reprogramming of myelopoiesis to reduce metastatic spread.Cancer cell · 2025Article
- Serglycin controls megakaryocyte retention of platelet factor 4 and influences megakaryocyte fate in bone marrow.Blood advances · 2025Article
- Engineered RAP-anchored copper-escorting liposomes for FDX1-targeted cuproptosis in glioblastoma therapy.Theranostics · 2025Article
- The winding road to platelet α-granules.Frontiers in cell and developmental biology · 2025Review
- Article
- Packaging of supplemented urokinase into alpha granules of in vitro-grown megakaryocytes for targeted nascent clot lysis.Blood advances · 2024Article
- A subset of megakaryocytes regulates development of hematopoietic stem cell precursors.The EMBO journal · 2024Article
- JA(c)K-in-the-platelet and M(i)PL fetch PF4.Blood · 2024Article
- Article
- Megakaryocyte Secreted Factors Regulate Bone Marrow Niche Cells During Skeletal Homeostasis, Aging, and Disease.Calcified tissue international · 2023Review
- Platelet Activation by Antisense Oligonucleotides (ASOs) in the Göttingen Minipig, including an Evaluation of Glycoprotein VI (GPVI) and Platelet Factor 4 (PF4) Ontogeny.Pharmaceutics · 2023Article
- Single platelet and megakaryocyte morpho-dynamics uncovered by multicolor reporter mouse strainsHaematologica · 2022Article
- The bone marrow niche from the inside out: how megakaryocytes are shaped by and shape hematopoiesis.Blood · 2022Review
- Differential Effects of Platelet Factor 4 (CXCL4) and Its Non-Allelic Variant (CXCL4L1) on Cultured Human Vascular Smooth Muscle Cells.International journal of molecular sciences · 2022Article
- Hemin induces autophagy in a leukemic erythroblast cell line through the LRP1 receptor.Bioscience reports · 2019Article
- Exploring the Extracellular Regulation of the Tumor Angiogenic Interaction Network Using a Systems Biology Model.Frontiers in physiology · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Platelet factor 4 (PF4) is a negative regulator of megakaryopoiesis, but its mechanism of action had not been addressed. Low-density lipoprotein (LDL) receptor-related protein-1 (LRP1) has been shown to mediate endothelial cell responses to PF4 and so we tested this receptor's importance in PF4's role in megakaryopoiesis. We found that LRP1 is absent from megakaryocyte-erythrocyte progenitor cells, is maximally present on large, polyploidy megakaryocytes, and near absent on platelets. Blocking LRP1 with either receptor-associated protein (RAP), an antagonist of LDL family member receptors, or specific anti-LRP1 antibodies reversed the inhibition of megakaryocyte colony growth by PF4. In addition, using shRNA to reduce LRP1 expression was able to restore megakaryocyte colony formation in bone marrow isolated from human PF4-overexpressing mice (hPF4(High)). Further, shRNA knockdown of LRP1 expression was able to limit the effects of PF4 on megakaryopoiesis. Finally, infusion of RAP into hPF4(High) mice was able to increase baseline platelet counts without affecting other lineages, suggesting that this mechanism is important in vivo. These studies extend our understanding of PF4's negative paracrine effect in megakaryopoiesis and its potential clinical implications as well as provide insights into the biology of LRP1, which is transiently expressed during megakaryopoiesis.
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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.