ArticleAging cell2012
MFG-E8 activates proliferation of vascular smooth muscle cells via integrin signaling.
Article in Aging cell, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers, 1 of them a synthesis that pooled it.
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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
62 citing papers in PubMed, 1 synthesis or guideline pooled it, 110 citations in OpenAlex.
- Hyperuricemia as an independent predictor of vascular complications and mortality in type 2 diabetes patients: a meta-analysis.PloS one · 2013Pooled it
- Neuro-Mechanical Regulation of Vascular Smooth Muscle Cell Behaviour Under Ageing-Associated Substrate Stiffness.Current issues in molecular biology · 2026Article
- Milk fat globule EGF and factor V/VIII domain containing (MFGE8) as a novel player in equine endometrial fibrosis.Scientific reports · 2026Article
- Collagen binding properties separate two functionally distinct subpopulations of milk extracellular vesicles regarding bone regenerative capacity.Materials today. Bio · 2025Article
- Potentiating microglial efferocytosis by MFG-E8 improves survival and neurological outcome after successful cardiopulmonary resuscitation in mice.Brain pathology (Zurich, Switzerland) · 2025Article
- Bioenergetic-related gene expression in the hippocampus predicts internalizing vs. externalizing behavior in an animal model of temperament.Frontiers in molecular neuroscience · 2025Article
- Plasma NOTCH3 and the risk of cardiovascular recurrence in patients with ischemic stroke.QJM : monthly journal of the Association of Physicians · 2024Article
- GHRH-stimulated pituitary small extracellular vesicles inhibit hepatocyte proliferation and IGF-1 expression by its cargo miR-375-3p.Journal of nanobiotechnology · 2024Article
- The regulation of MFG-E8 on the mitophagy in diabetic sarcopenia via the HSPA1L-Parkin pathway and the effect of D-pinitol.Journal of cachexia, sarcopenia and muscle · 2024Article
- Enhanced vasorin signaling mitigates adverse cardiovascular remodeling.Aging medicine (Milton (N.S.W)) · 2024Review
- Eugenol Inhibits Ox-LDL-Induced Proliferation and Migration of Human Vascular Smooth Muscle Cells by Inhibiting the Ang II/MFG-E8/MCP-1 Signaling Cascade.Journal of inflammation research · 2024Article
- Remodeling of the Cardiac Extracellular Matrix Proteome During Chronological and Pathological Aging.Molecular & cellular proteomics : MCP · 2024Article
- Human cell-expressed tag-free rhMFG-E8 as an effective radiation mitigator.Scientific reports · 2023Article
- Targeting MFGE8 secreted by cancer-associated fibroblasts blocks angiogenesis and metastasis in esophageal squamous cell carcinoma.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Single-cell RNA sequencing reveals the vascular smooth muscle cell phenotypic landscape in aortic aneurysm.Cell communication and signaling : CCS · 2023Article
- Introducing Circulating Vasculature-Related Transcripts as Biomarkers in Coronary Artery Disease.Molecular diagnosis & therapy · 2023Article
- Arteriolar neuropathology in cerebral microvascular disease.Neuropathology and applied neurobiology · 2023Review
- Review
- MFG-E8 stabilized by deubiquitinase USP14 suppresses cigarette smoke-induced ferroptosis in bronchial epithelial cells.Cell death & disease · 2023Article
- How vascular smooth muscle cell phenotype switching contributes to vascular disease.Cell communication and signaling : CCS · 2022Review
2 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
An accumulation of milk fat globule EGF-8 protein (MFG-E8) occurs within the context of arterial wall inflammatory remodeling during aging, hypertension, diabetes mellitus, or atherosclerosis. MFG-E8 induces VSMC invasion, but whether it affects VSMC proliferation, a salient feature of arterial inflammation, is unknown. Here, we show that in the rat arterial wall in vivo, PCNA and Ki67, markers of cell cycle activation, increase with age between 8 and 30 months. In fresh and early passage VSMC isolated from old aortae, an increase in CDK4 and PCNA, an increase in the acceleration of cell cycle S and G2 phases, decrease in the G1/G0 phase, and an increase in PDGF and its receptors confer elevated proliferative capacity, compared to young VSMC. Increased coexpression and physical interaction of MFG-E8 and integrin αvβ5 occur with aging in both the rat aortic wall in vivo and in VSMC in vitro. In young VSMC in vitro, MFG-E8 added exogenously, or overexpressed endogenously, triggers phosphorylation of ERK1/2, augmented levels of PCNA and CDK4, increased BrdU incorporation, and promotes proliferation, via αvβ5 integrins. MFG-E8 silencing, or its receptor inhibition, or the blockade of ERK1/2 phosphorylation in these cells reduces PCNA and CDK4 levels and decelerates the cell cycle S phase, conferring a reduction in proliferative capacity. Collectively, these results indicate that MFG-E8 in a dose-dependent manner coordinates the expression of cell cycle molecules and facilitates VSMC proliferation via integrin/ERK1/2 signaling. Thus, an increase in MFG-E8 signaling is a mechanism of the age-associated increase in aortic VSMC proliferation.
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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.