ArticlePloS one2012
Proteomic analysis of aorta and protective effects of grape seed procyanidin B2 in db/db mice reveal a critical role of milk fat globule epidermal growth factor-8 in diabetic arterial damage.
Article in PloS one, 2012. 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, 55 citations in OpenAlex.
- Adipose tissue-derived MFG-E8 promotes hepatic inflammation and fibrosis through macrophage activation in a mouse MASH model.npj metabolic health and disease · 2026Article
- 3,3'-Diindolylmethane blocks the dissemination of gastric cancer cells in the peritoneal cavity through the MFGE8-MAPK/ERK signaling pathway.Cancer cell international · 2025Article
- The application of procyanidins in diabetes and its complications: a review of preclinical studies.Frontiers in pharmacology · 2025Review
- Bioactive Flavonoids in Protecting Against Endothelial Dysfunction and Atherosclerosis.Handbook of experimental pharmacology · 2025Review
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- The multiple actions of grape and its polyphenols on female reproductive processes with an emphasis on cell signalling.Frontiers in endocrinology · 2023Review
- Inflammatory Role of Milk Fat Globule-Epidermal Growth Factor VIII in Age-Associated Arterial Remodeling.Journal of the American Heart Association · 2022Article
- MFG-E8 promotes osteogenic transdifferentiation of smooth muscle cells and vascular calcification by regulating TGF-β1 signaling.Communications biology · 2022Article
- Procyanidin B2 Reduces Vascular Calcification through Inactivation of ERK1/2-RUNX2 Pathway.Antioxidants (Basel, Switzerland) · 2021Article
- MFG-E8 Regulates Vascular Smooth Muscle Cell Migration Through Dose-Dependent Mediation of Actin Polymerization.Journal of the American Heart Association · 2021Article
- Autoregulation of insulin receptor signaling through MFGE8 and the αvβ5 integrin.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Computational and In Vitro Investigation of (-)-Epicatechin and Proanthocyanidin B2 as Inhibitors of Human Matrix Metalloproteinase 1.Biomolecules · 2020Article
- A rare missense variant in the milk fat globule-EGF factor 8 (MFGE8) increases T2DM susceptibility and cardiovascular disease risk with population-specific effects.Acta diabetologica · 2020Article
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- Polymorphisms of MFGE8 are associated with susceptibility and clinical manifestations through gene expression modulation in Koreans with systemic lupus erythematosus.Scientific reports · 2019Article
- Proanthocyanidin B2 attenuates high-glucose-induced neurotoxicity of dorsal root ganglion neurons through the PI3K/Akt signaling pathway.Neural regeneration research · 2018Article
- Mfge8 regulates enterocyte lipid storage by promoting enterocyte triglyceride hydrolase activity.JCI insight · 2016Article
- Critical Role of FoxO1 in Granulosa Cell Apoptosis Caused by Oxidative Stress and Protective Effects of Grape Seed Procyanidin B2.Oxidative medicine and cellular longevity · 2016Article
- Investigation of the Effects and Mechanisms of Mai Tong Formula on Lower Limb Macroangiopathy in a Spontaneous Diabetic Rat Model.Journal of diabetes research · 2016Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAtherosclerosis is one of the major complications of type 2 diabetic patients (T2DM), leading to morbidity and mortality. Grape seed procyanidin B2 (GSPB2) has demonstrated protective effect against atherosclerosis, which is believed to be, at least in part, a result of its antioxidative effects. The aim of this study is to identify the target protein of GSPB2 responsible for the protective effect against atherosclerosis in patients with DM. METHODS AND
resultsGSPB2 (30 mg/kg body weight/day) were administrated to db/db mice for 10 weeks. Proteomics of the aorta extracts by iTRAQ analysis was obtained from db/db mice. The results showed that expression of 557 proteins were either up- or down-regulated in the aorta of diabetic mice. Among those proteins, 139 proteins were normalized by GSPB2 to the levels comparable to those in control mice. Among the proteins regulated by GSPB2, the milk fat globule epidermal growth factor-8 (MFG-E8) was found to be increased in serum level in T2DM patients; the serum level of MFG-E8 was positively correlated with carotid-femoral pulse wave velocity (CF-PWV). Inhibition of MFG-E8 by RNA interference significantly suppressed whereas exogenous recombinant MFG-E8 administration exacerbated atherogenesis the db/db mice. To gain more insights into the mechanism of action of MFG-E8, we investigated the effects of MFG-E8 on the signal pathway involving the extracellular signal-regulated kinase (ERK) and monocyte chemoattractant protein-1 (MCP-1). Treatment with recombinant MFG-E8 led to increased whereas inhibition of MFG-E8 to decreased expression of MCP-1 and phosphorylation of ERK1/2.
conclusionOur data suggests that MFG-E8 plays an important role in atherogenesis in diabetes through both ERK and MCP-1 signaling pathways. GSPB2, a well-studied antioxidant, significantly inhibited the arterial wall changes favoring atherogenesis in db/db mice by down-regulating MFG-E8 expression in aorta and its serum level. Measuring MFG-E8 serum level could be a useful clinical surrogate prognosticating atherogenesis in DM patients.
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