ArticlePloS one2013
Spry1 and Spry4 differentially regulate human aortic smooth muscle cell phenotype via Akt/FoxO/myocardin signaling.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.
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Who cites it
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 48 citations in OpenAlex.
- An integrative meta-analysis of microRNAs in hepatocellular carcinoma.Genomics, proteomics & bioinformatics · 2013Pooled it
- Myeloid Ecotropic Viral Integration Site 1 Promotes Vascular Smooth Muscle Differentiation through Activation of Myocardin.bioRxiv : the preprint server for biology · 2026Article
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- Effects and mechanisms of trifolin on attenuating hypertension-induced vascular smooth muscle cell proliferation and collagen deposition in vivo and in vitro.Scientific reports · 2025Article
- Colchicine reduces neointima formation and VSMC phenotype transition by modulating SRF-MYOCD activation and autophagy.Acta pharmacologica Sinica · 2025Article
- Mechanisms of nebivolol-mediated effects on bFGF-induced vascular smooth muscle cell proliferation and migration.Current research in pharmacology and drug discovery · 2025Article
- Efficient improvement of the proliferation, differentiation, and anti-arthritic capacity of mesenchymal stem cells by simply culturing on the immobilized FGF2 derived peptide, 44-ERGVVSIKGV-53.Journal of advanced research · 2024Article
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- Sprouty1 has a protective role in atherogenesis and modifies the migratory and inflammatory phenotype of vascular smooth muscle cells.Atherosclerosis · 2023Article
- NCOR1 maintains the homeostasis of vascular smooth muscle cells and protects against aortic aneurysm.Cell death and differentiation · 2023Article
- Molecular Mechanisms in Genetic Aortopathy-Signaling Pathways and Potential Interventions.International journal of molecular sciences · 2023Review
- The role of phosphoinositide 3-kinases in immune-inflammatory responses: potential therapeutic targets for abdominal aortic aneurysm.Cell cycle (Georgetown, Tex.) · 2022Review
- Fibroblast growth factor receptor signalling dysregulation and targeting in breast cancer.Open biology · 2022Review
- Integrated bioinformatics, network pharmacology, and artificial intelligence to predict the mechanism of celastrol against muscle atrophy caused by colorectal cancer.Frontiers in genetics · 2022Article
- Vascular smooth muscle cells in atherosclerosis: time for a re-assessment.Cardiovascular research · 2021Review
- RhoGDI1-Cdc42 Signaling Is Required for PDGF-BB-Induced Phenotypic Transformation of Vascular Smooth Muscle Cells and Neointima Formation.Biomedicines · 2021Article
- Loss of FoxO3a prevents aortic aneurysm formation through maintenance of VSMC homeostasis.Cell death & disease · 2021Article
- FGF, Mechanism of Action, Role in Parkinson's Disease, and Therapeutics.Frontiers in pharmacology · 2021Review
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Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundChanges in the vascular smooth muscle cell (VSMC) contractile phenotype occur in pathological states such as restenosis and atherosclerosis. Multiple cytokines, signaling through receptor tyrosine kinases (RTK) and PI3K/Akt and MAPK/ERK pathways, regulate these phenotypic transitions. The Spry proteins are feedback modulators of RTK signaling, but their specific roles in VSMC have not been established. METHODOLOGY/PRINCIPAL
findingsHere, we report for the first time that Spry1, but not Spry4, is required for maintaining the differentiated state of human VSMC in vitro. While Spry1 is a known MAPK/ERK inhibitor in many cell types, we found that Spry1 has little effect on MAPK/ERK signaling but increases and maintains Akt activation in VSMC. Sustained Akt signaling is required for VSMC marker expression in vitro, while ERK signaling negatively modulates Akt activation and VSMC marker gene expression. Spry4, which antagonizes both MAPK/ERK and Akt signaling, suppresses VSMC differentiation marker gene expression. We show using siRNA knockdown and ChIP assays that FoxO3a, a downstream target of PI3K/Akt signaling, represses myocardin promoter activity, and that Spry1 increases, while Spry4 decreases myocardin mRNA levels.
conclusionsTogether, these data indicate that Spry1 and Spry4 have opposing roles in VSMC phenotypic modulation, and Spry1 maintains the VSMC differentiation phenotype in vitro in part through an Akt/FoxO/myocardin pathway.
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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.