ArticleAntioxidants & redox signaling2017
CD47 and Nox1 Mediate Dynamic Fluid-Phase Macropinocytosis of Native LDL.
Article in Antioxidants & redox signaling, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 33 citations in OpenAlex.
- The CD47 signaling axis regulates the formation and vulnerability of atherosclerotic plaques: mechanism analysis and targeting strategies.Frontiers in immunology · 2026Review
- Role of Matricellular Proteins in Endothelial Cell Inflammation and Atherosclerosis.Antioxidants (Basel, Switzerland) · 2025Review
- CD47-mediated tumor microenvironment remodeling: a central mechanism in immune evasion.Acta biochimica et biophysica Sinica · 2025Review
- Membrane Ruffles: Composition, Function, Formation and Visualization.International journal of molecular sciences · 2024Review
- Tolerating CD47.Clinical and translational medicine · 2024Review
- Matricellular proteins in atherosclerosis development.Matrix biology : journal of the International Society for Matrix Biology · 2023Review
- Unconventional Functions of Amino Acid Transporters: Role in Macropinocytosis (SLC38A5/SLC38A3) and Diet-Induced Obesity/Metabolic Syndrome (SLC6A19/SLC6A14/SLC6A6).Biomolecules · 2022Review
- Pinocytotic engulfment of lipoproteins by macrophages.Frontiers in cardiovascular medicine · 2022Review
- Thrombospondin-1 aggravates colonic mucosal inflammatory injuries via promoting the differentiation of CD11cAnnals of translational medicine · 2021Article
- CD47 and thrombospondin-1 regulation of mitochondria, metabolism, and diabetes.American journal of physiology. Cell physiology · 2021Review
- Visualizing Membrane Ruffle Formation using Scanning Electron Microscopy.Journal of visualized experiments : JoVE · 2021Article
- Oxidatively Modified LDL Suppresses Lymphangiogenesis via CD36 Signaling.Antioxidants (Basel, Switzerland) · 2021Article
- Role of thrombospondin‑1 and thrombospondin‑2 in cardiovascular diseases (Review).International journal of molecular medicine · 2020Review
- Interleukin 10 promotes macrophage uptake of HDL and LDL by stimulating fluid-phase endocytosis.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2020Article
- Loss of GTPase activating protein neurofibromin stimulates paracrine cell communication via macropinocytosis.Redox biology · 2019Article
- Constitutive and stimulated macropinocytosis in macrophages: roles in immunity and in the pathogenesis of atherosclerosis.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2019Review
- PKCδ stimulates macropinocytosis via activation of SSH1-cofilin pathway.Cellular signalling · 2019Article
- Identification of novel macropinocytosis inhibitors using a rational screen of Food and Drug Administration-approved drugs.British journal of pharmacology · 2018Article
- Role of Thrombospondin-1 in Mechanotransduction and Development of Thoracic Aortic Aneurysm in Mouse and Humans.Circulation research · 2018Article
- PKCδ-Mediated Nox2 Activation Promotes Fluid-Phase Pinocytosis of Antigens by Immature Dendritic Cells.Frontiers in immunology · 2018Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
Abstract
aimsMacropinocytosis has been implicated in cardiovascular and other disorders, yet physiological factors that initiate fluid-phase internalization and the signaling mechanisms involved remain poorly identified. The present study was designed to examine whether matrix protein thrombospondin-1 (TSP1) stimulates macrophage macropinocytosis and, if so, to investigate the potential signaling mechanism involved.
resultsTSP1 treatment of human and murine macrophages stimulated membrane ruffle formation and pericellular solute internalization by macropinocytosis. Blockade of TSP1 cognate receptor CD47 and NADPH oxidase 1 (Nox1) signaling, inhibition of phosphoinositide 3-kinase, and transcriptional knockdown of myotubularin-related protein 6 abolished TSP1-induced macropinocytosis. Our results demonstrate that Nox1 signaling leads to dephosphorylation of actin-binding protein cofilin at Ser-3, actin remodeling, and macropinocytotic uptake of unmodified native low-density lipoprotein (nLDL), leading to foam cell formation. Finally, peritoneal chimera studies suggest the role of CD47 in macrophage lipid macropinocytosis in hypercholesterolemic ApoE INNOVATION: Activation of a previously unidentified TSP1-CD47 signaling pathway in macrophages stimulates direct receptor-independent internalization of nLDL, leading to significant lipid accumulation and foam cell formation. These findings reveal a new paradigm in which delimited Nox1-mediated redox signaling, independent of classical lipid oxidation, contributes to early propagation of vascular inflammatory disease.
conclusionsThe findings of the present study demonstrate a new mechanism of solute uptake with implications for a wide array of cell types, including macrophages, dendritic cells, and cancer cells, and multiple pathological conditions in which matrix proteins are upregulated. Antioxid. Redox Signal. 26, 886-901.
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