ArticleThe American journal of pathology2014
Ras-Mek-Erk signaling regulates Nf1 heterozygous neointima formation.
Article in The American journal of pathology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 31 citations in OpenAlex.
- Neurovascular Issues in Neurofibromatosis Type I: Focus on Intracranial Stenosis.Life (Basel, Switzerland) · 2026Review
- Review
- The Nf1-Q181X point mutation induces M2 macrophage polarization via the AKT/STAT pathway to promote smooth muscle cell proliferation and migration.Molecular biology reports · 2024Article
- Cerebral arteriopathies of childhood and stroke - A focus on systemic arteriopathies and pediatric fibromuscular dysplasia (FMD).Vascular medicine (London, England) · 2024Review
- MEK inhibitors: a promising targeted therapy for cardiovascular disease.Frontiers in cardiovascular medicine · 2024Review
- Cardiac pericyte reprogramming by MEK inhibition promotes arteriologenesis and angiogenesis of the ischemic heart.The Journal of clinical investigation · 2022Article
- Childhood stroke.Nature reviews. Disease primers · 2022Review
- PLD1 promotes reactive oxygen species production in vascular smooth muscle cells and injury-induced neointima formation.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2022Article
- MEK inhibition exerts temporal and myeloid cell-specific effects in the pathogenesis of neurofibromatosis type 1 arteriopathy.Scientific reports · 2021Article
- MEK inhibitors - novel targeted therapies of neurofibromatosis associated benign and malignant lesions.Biomarker research · 2021Review
- An update on the central nervous system manifestations of neurofibromatosis type 1.Acta neuropathologica · 2020Review
- Loss of GTPase activating protein neurofibromin stimulates paracrine cell communication via macropinocytosis.Redox biology · 2019Article
- Neurofibromin 1 expression is negatively correlated with malignancy and prognosis of epithelial ovarian cancer.International journal of clinical and experimental pathology · 2019Article
- Neurofibromin Deficiency Induces Endothelial Cell Proliferation and Retinal Neovascularization.Investigative ophthalmology & visual science · 2018Article
- Genetic and Epigenetic Regulation of Aortic Aneurysms.BioMed research international · 2017Review
- Neurofibromin is a novel regulator of Ras-induced reactive oxygen species production in mice and humans.Free radical biology & medicine · 2016Article
- Nf1+/- monocytes/macrophages induce neointima formation via CCR2 activation.Human molecular genetics · 2016Article
- Hyperactive RAS/PI3-K/MAPK Signaling Cascade in Migration and Adhesion of Nf1 Haploinsufficient Mesenchymal Stem/Progenitor Cells.International journal of molecular sciences · 2015Article
- Neuronal NF1/RAS regulation of cyclic AMP requires atypical PKC activation.Human molecular genetics · 2014Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Neurofibromatosis type 1 (NF1) results from mutations in the NF1 tumor-suppressor gene, which encodes neurofibromin, a negative regulator of diverse Ras signaling cascades. Arterial stenosis is a nonneoplastic manifestation of NF1 that predisposes some patients to debilitating morbidity and sudden death. Recent murine studies demonstrate that Nf1 heterozygosity (Nf1(+/-)) in monocytes/macrophages significantly enhances intimal proliferation after arterial injury. However, the downstream Ras effector pathway responsible for this phenotype is unknown. Based on in vitro assays demonstrating enhanced extracellular signal-related kinase (Erk) signaling in Nf1(+/-) macrophages and vascular smooth muscle cells and in vivo evidence of Erk amplification without alteration of phosphatidylinositol 3-kinase signaling in Nf1(+/-) neointimas, we tested the hypothesis that Ras-Erk signaling regulates intimal proliferation in a murine model of NF1 arterial stenosis. By using a well-established in vivo model of inflammatory cell migration and standard cell culture, neurofibromin-deficient macrophages demonstrate enhanced sensitivity to growth factor stimulation in vivo and in vitro, which is significantly diminished in the presence of PD0325901, a specific inhibitor of Ras-Erk signaling in phase 2 clinical trials for cancer. After carotid artery injury, Nf1(+/-) mice demonstrated increased intimal proliferation compared with wild-type mice. Daily administration of PD0325901 significantly reduced Nf1(+/-) neointima formation to levels of wild-type mice. These studies identify the Ras-Erk pathway in neurofibromin-deficient macrophages as the aberrant pathway responsible for enhanced neointima formation.
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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.