ArticlePharmacological research2017
Sulforaphane inhibits platelet-derived growth factor-induced vascular smooth muscle cell proliferation by targeting mTOR/p70S6kinase signaling independent of Nrf2 activation.
Article in Pharmacological research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 53 citations in OpenAlex.
- Inhibition of smooth muscle phenotypic modulation by bardoxolone methyl, omaveloxolone, and cinnamaldehyde is Nrf-2 dependent.Advances in redox research · 2026Article
- Sulforaphane: a natural organosulfur having potential to modulate apoptosis and survival signalling in cancer.Discover oncology · 2025Review
- TET1 Regulates Nestin Expression and Human Airway Smooth Muscle Proliferation.American journal of respiratory cell and molecular biology · 2024Article
- ABCA4 mediated traumatic proliferative vitreoretinopathy associated with PI3K/Akt signaling pathway.Heliyon · 2024Article
- Hsa_circ_0031891 targets miR-579-3p to enhance HMGB1 expression and regulate PDGF-BB-induced human aortic vascular smooth muscle cell proliferation, migration, and dedifferentiation.Naunyn-Schmiedeberg's archives of pharmacology · 2024Article
- Inhibition of p90RSK Ameliorates PDGF-BB-Mediated Phenotypic Change of Vascular Smooth Muscle Cell and Subsequent Hyperplasia of Neointima.International journal of molecular sciences · 2023Article
- Article
- The Anti-Inflammatory Effects of Iberin on TNF-α-Stimulated Human Oral Epithelial Cells: In Vitro Research.Biomedicines · 2022Article
- 6-(Methylsulfinyl) Hexyl Isothiocyanate Inhibits IL-6 and CXCL10 Production in TNF-α-Stimulated Human Oral Epithelial Cells.Current issues in molecular biology · 2022Article
- pH-Responsive Nanoparticles for Delivery of Paclitaxel to the Injury Site for Inhibiting Vascular Restenosis.Pharmaceutics · 2022Article
- Theaflavin-3,3'-Digallate from Black Tea Inhibits Neointima Formation Through Suppression of the PDGFRβ Pathway in Vascular Smooth Muscle Cells.Frontiers in pharmacology · 2022Article
- NRF2: A crucial regulator for mitochondrial metabolic shift and prostate cancer progression.Frontiers in physiology · 2022Review
- miR‑125a‑5p and miR‑7 inhibits the proliferation, migration and invasion of vascular smooth muscle cell by targeting EGFR.Molecular medicine reports · 2021Article
- Research advance of Nrf2 on atherosclerosis by regulating vascular smooth muscle cell.Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2021Review
- The isothiocyanate sulforaphane inhibits mTOR in an NRF2-independent manner.Phytomedicine : international journal of phytotherapy and phytopharmacology · 2021Article
- Imatinib improves insulin resistance and inhibits injury-induced neointimal hyperplasia in high fat diet-fed mice.European journal of pharmacology · 2021Article
- Nrf2-interacting nutrients and COVID-19: time for research to develop adaptation strategies.Clinical and translational allergy · 2020Review
- Activation of AMPK by Telmisartan Decreases Basal and PDGF-stimulated VSMC Proliferation via Inhibiting the mTOR/p70S6K Signaling Axis.Journal of Korean medical science · 2020Article
- AKT/FOXO1 axis links cross-talking of endothelial cell and pericyte in TIE2-mutated venous malformations.Cell communication and signaling : CCS · 2020Article
- Acute antioxidant and cytoprotective effects of sulforaphane in brain endothelial cells and astrocytes during inflammation and excitotoxicity.Pharmacology research & perspectives · 2020Article
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 2 countries.
Funding
Abstract
Activation of nuclear factor erythroid 2-related factor 2 (Nrf2, a transcription factor) and/or inhibition of mammalian target of rapamycin (mTOR) are implicated in the suppression of vascular smooth muscle cell (VSMC) proliferation. The present study has examined the likely regulatory effects of sulforaphane (SFN, an antioxidant) on Nrf2 activation and platelet-derived growth factor (PDGF)-induced mTOR signaling in VSMCs. Using human aortic VSMCs, nuclear extraction and siRNA-mediated downregulation studies were performed to determine the role of Nrf2 on SFN regulation of PDGF-induced proliferative signaling. Immunoprecipitation and/or immunoblot studies were carried out to determine how SFN regulates PDGF-induced mTOR/p70S6K/S6 versus ERK and Akt signaling. Immunohistochemical analysis was performed to determine SFN regulation of S6 phosphorylation in the injured mouse femoral artery. SFN (5μM) inhibits PDGF-induced activation of mTOR without affecting mTOR association with raptor in VSMCs. While SFN inhibits PDGF-induced phosphorylation of p70S6K and 4E-BP1 (downstream targets of mTOR), it does not affect ERK or Akt phosphorylation. In addition, SFN diminishes exaggerated phosphorylation of S6 ribosomal protein (a downstream target of p70S6K) in VSMCs in vitro and in the neointimal layer of injured artery in vivo. Although SFN promotes Nrf2 accumulation to upregulate cytoprotective genes (e.g., heme oxygenase-1 and thioredoxin-1), downregulation of endogenous Nrf2 by target-specific siRNA reveals an Nrf2-independent effect for SFN-mediated inhibition of mTOR/p70S6K/S6 signaling and suppression of VSMC proliferation. Strategies that utilize local delivery of SFN at the lesion site may limit restenosis after angioplasty by targeting mTOR/p70S6K/S6 axis in VSMCs independent of Nrf2 activation.
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Registered trials
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