ArticlePloS one2013
Transforming growth factor β inhibits platelet derived growth factor-induced vascular smooth muscle cell proliferation via Akt-independent, Smad-mediated cyclin D1 downregulation.
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 21 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
21 citing papers in PubMed, 42 citations in OpenAlex.
- Therapeutic effects of PDGF-AB/BB against cellular senescence in human intervertebral disc.eLife · 2025Article
- Selenomethionine inhibits the proliferation of hypoxia-induced pulmonary artery smooth muscle cells by inhibiting ROS and HIF-1α-ACE-AngII axis.Scientific reports · 2025Article
- Therapeutic effects of PDGF-AB/BB against cellular senescence in human intervertebral disc.bioRxiv : the preprint server for biology · 2025Article
- Insulin-like growth factor family and its impact on pulmonary arterial hypertension: a review.Frontiers in physiology · 2025Review
- Novel Factors Regulating Proliferation, Migration, and Differentiation of Fibroblasts, Keratinocytes, and Vascular Smooth Muscle Cells during Wound Healing.Biomedicines · 2024Review
- Transcription factors: key regulatory targets of vascular smooth muscle cell in atherosclerosis.Molecular medicine (Cambridge, Mass.) · 2023Review
- Macrophages and Foam Cells: Brief Overview of Their Role, Linkage, and Targeting Potential in Atherosclerosis.Biomedicines · 2021Review
- Current knowledge of Krüppel-like factor 5 and vascular remodeling: providing insights for therapeutic strategies.Journal of molecular cell biology · 2021Review
- Dasatinib induces a dramatic response in a child with refractory juvenile xanthogranuloma with a novel MRC1-PDGFRB fusion.Blood advances · 2020Article
- Excessive Production of Transforming Growth Factor β1 Causes Mural Cell Depletion From Cerebral Small Vessels.Frontiers in aging neuroscience · 2020Article
- SPARCL1 promotes C2C12 cell differentiation via BMP7-mediated BMP/TGF-β cell signaling pathway.Cell death & disease · 2019Article
- Long non-coding RNA SNHG16 regulates human aortic smooth muscle cell proliferation and migration via sponging miR-205 and modulating Smad2.Journal of cellular and molecular medicine · 2019Article
- TGFβ, smooth muscle cells and coronary artery disease: a review.Cellular signalling · 2019Review
- Contribution of p62/SQSTM1 to PDGF-BB-induced myofibroblast-like phenotypic transition in vascular smooth muscle cells lacking Smpd1 gene.Cell death & disease · 2018Article
- Integrated Analysis of LncRNA-mRNA Co-Expression Profiles in Patients with Moyamoya Disease.Scientific reports · 2017Article
- Pdgfrb is a direct regulatory target of TGFβ signaling in atrioventricular cushion mesenchymal cells.PloS one · 2017Article
- Noncoding RNAs in smooth muscle cell homeostasis: implications in phenotypic switch and vascular disorders.Pflugers Archiv : European journal of physiology · 2016Review
- Mitochondrial dynamics, mitophagy and cardiovascular disease.The Journal of physiology · 2016Review
- Relation between anti-atherosclerotic effects of IRAK4 and modulation of vascular smooth muscle cell phenotype in diabetic rats.American journal of translational research · 2016Article
- KLF5 inhibits angiogenesis in PTEN-deficient prostate cancer by attenuating AKT activation and subsequent HIF1α accumulation.Molecular cancer · 2015Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
In adult tissue, vascular smooth muscle cells (VSMCs) exist in a differentiated phenotype, which is defined by the expression of contractile proteins and lack of proliferation. After vascular injury, VSMC adopt a synthetic phenotype associated with proliferation, migration and matrix secretion. The transition between phenotypes is a consequence of the extracellular environment, and in particular, is regulated by agonists such as the pro-differentiating cytokine transforming growth factor β (TGFβ) and the pro-proliferative cytokine platelet derived growth factor (PDGF). In this study, we investigated the interplay between TGFβ and PDGF with respect to their ability to regulate VSMC proliferation. Stimulation of human aortic VSMC with TGFβ completely blocked proliferation induced by all isoforms of PDGF, as measured by DNA synthesis and total cell number. Mechanistically, PDGF-induced Cyclin D1 mRNA and protein expression was inhibited by TGFβ. TGFβ had no effect on PDGF activation of its receptor and ERK1/2, but inhibited Akt activation. However, constitutively active Akt did not reverse the inhibitory effect of TGFβ on Cyclin D1 expression even though inhibition of the proteasome blocked the effect of TGFβ. siRNA against Smad4 completely reversed the inhibitory effect of TGFβ on PDGF-induced Cyclin D1 expression and restored proliferation in response to PDGF. Moreover, siRNA against KLF5 prevented Cyclin D1 upregulation by PDGF and overexpression of KLF5 partially reversed TGFβ-induced inhibition of Cyclin D1 expression. Taken together, our results demonstrate that KLF5 is required for PDGF-induced Cyclin D1 expression, which is inhibited by TGFβ via a Smad dependent mechanism, resulting in arrest of VSMCs in the G1 phase of the cell cycle.
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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.