ArticleProceedings of the National Academy of Sciences of the United States of America2013
Mfge8 suppresses airway hyperresponsiveness in asthma by regulating smooth muscle contraction.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 61 citations in OpenAlex.
- The MFGE8/integrin β3 axis mitigates experimental neutrophilic asthma by suppressing NLRP3-Caspase-1 pathway-mediated NETosis.Respiratory research · 2025Article
- Mfge8 is expressed by pericytes in gastric antrum submucosa from patients with obesity.American journal of physiology. Cell physiology · 2023Article
- Oxidative Stress and Inflammation in Acute and Chronic Lung Injuries.Antioxidants (Basel, Switzerland) · 2023Review
- Progranulin deficiency suppresses allergic asthma and enhances efferocytosis via PPAR-γ/MFG-E8 regulation in macrophages.Immunity, inflammation and disease · 2023Article
- Down-regulation of miR-140-3p is a cause of the interlukin-13-induced up-regulation of RhoA protein in bronchial smooth muscle cells.Small GTPases · 2022Article
- MFG-E8 Knockout Aggravated Nonalcoholic Steatohepatitis by Promoting the Activation of TLR4/NF-Mediators of inflammation · 2022Article
- Vascular involvement in chronic thromboembolic pulmonary hypertension is associated with spirometry obstructive impairment.BMC pulmonary medicine · 2021Article
- What's the deal with efferocytosis and asthma?Trends in immunology · 2021Review
- Integrin α2β1 regulates collagen I tethering to modulate hyperresponsiveness in reactive airway disease models.The Journal of clinical investigation · 2021Article
- Mfge8 attenuates human gastric antrum smooth muscle contractions.Journal of muscle research and cell motility · 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
- Extracellular vesicles produced by bone marrow mesenchymal stem cells attenuate renal fibrosis, in part by inhibiting the RhoA/ROCK pathway, in a UUO rat model.Stem cell research & therapy · 2020Article
- RhoA/Rho-kinases in asthma: from pathogenesis to therapeutic targets.Clinical & translational immunology · 2020Review
- Epigenome-wide association of father's smoking with offspring DNA methylation: a hypothesis-generating study.Environmental epigenetics · 2019Article
- Synovial fluid and plasma levels of milk fat globule-epidermal growth factor 8 are inversely correlated with radiographic severity of knee osteoarthritis.The Journal of international medical research · 2019Article
- Arhgef12 drives IL17A-induced airway contractility and airway hyperresponsiveness in mice.JCI insight · 2018Article
- Soluble ST2 regulation by rhinovirus and 25(OH)-vitamin D3 in the blood of asthmatic children.Clinical and experimental immunology · 2018Article
- Inflammatory bone loss associated with MFG-E8 deficiency is rescued by teriparatide.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2018Article
- Identification of novel target genes in human lung tissue involved in chronic obstructive pulmonary disease.International journal of chronic obstructive pulmonary disease · 2018Article
- Effect of Processing Intensity on Immunologically Active Bovine Milk Serum Proteins.Nutrients · 2017Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
Airway obstruction is a hallmark of allergic asthma and is caused primarily by airway smooth muscle (ASM) hypercontractility. Airway inflammation leads to the release of cytokines that enhance ASM contraction by increasing ras homolog gene family, member A (RhoA) activity. The protective mechanisms that prevent or attenuate the increase in RhoA activity have not been well studied. Here, we report that mice lacking the gene that encodes the protein Milk Fat Globule-EGF factor 8 (Mfge8(-/-)) develop exaggerated airway hyperresponsiveness in experimental models of asthma. Mfge8(-/-) ASM had enhanced contraction after treatment with IL-13, IL-17A, or TNF-α. Recombinant Mfge8 reduced contraction in murine and human ASM treated with IL-13. Mfge8 inhibited IL-13-induced NF-κB activation and induction of RhoA. Mfge8 also inhibited rapid activation of RhoA, an effect that was eliminated by an inactivating point mutation in the RGD integrin-binding site in recombinant Mfge8. Human subjects with asthma had decreased Mfge8 expression in airway biopsies compared with healthy controls. These data indicate that Mfge8 binding to integrin receptors on ASM opposes the effect of allergic inflammation on RhoA activity and identify a pathway for specific inhibition of ASM hypercontractility in asthma.
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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.