ArticleCellular signalling2016
A crosstalk between TGF-β/Smad3 and Wnt/β-catenin pathways promotes vascular smooth muscle cell proliferation.
Article in Cellular signalling, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.
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Who cites it
73 citing papers in PubMed, 131 citations in OpenAlex.
- Neointimal hyperplasia and vascular restenosis: from molecular mechanisms to therapeutic interventions.Molecular biomedicine · 2026Review
- Wnt/β-Catenin Pathway and Hydraulic Calcium Silicate-Based Cements: A Narrative Review.Dentistry journal · 2026Review
- EndMT in vascular cognitive impairment and dementia: mechanisms, evidence gaps, and therapeutic opportunities.Molecular medicine (Cambridge, Mass.) · 2026Review
- Identification of Mitochondrial Signature Biomarkers and Molecular Mechanisms in Atherosclerotic Tissues and Blood: Combined Single-Cell and Bulk RNA Sequencing Analysis.Molecular neurobiology · 2026Article
- A prevalent disease-associated SNP in the humanNAR molecular medicine · 2026Article
- Rewired DDR-TGF-β-β-catenin-PD-L1 axis accelerates progression and shapes therapy in human papillomavirus-driven cancer.Frontiers in immunology · 2026Review
- Dynamic transcriptional and epigenetic changes define postnatal tendon growth.PLoS genetics · 2025Article
- Rhein alleviates renal interstitial fibrosis by inhibiting Smad3 phosphorylation in TGF-Chinese herbal medicines · 2025Article
- ACVR2A facilitates trophoblast cell invasion through TCF7/c-JUN pathway in pre-eclampsia progression.eLife · 2025Article
- Elevated Expression ofBiomedicines · 2025Article
- Impact of the Transforming Growth Factor β (TGF-β) on Brain Aneurysm Formation and Development: A Literature Review.Cellular and molecular neurobiology · 2025Review
- JOSD2 inhibits angiotensin II-induced vascular remodeling by deubiquitinating and stabilizing SMAD7.Acta pharmacologica Sinica · 2025Article
- Wnt signaling pathways in biology and disease: mechanisms and therapeutic advances.Signal transduction and targeted therapy · 2025Review
- The Crosstalk Between Endothelial Cells, Smooth Muscle Cells, and Macrophages in Atherosclerosis.International journal of molecular sciences · 2025Review
- Pterostilbene mitigates experimental pulmonary arterial hypertension by inhibiting endothelial-to-mesenchymal transition.Frontiers in pharmacology · 2025Article
- CDK4/6 and BET inhibitors synergistically suppress pancreatic tumor growth and epithelial-to-mesenchymal transition by regulating the GSK3β-mediated Wnt/β-catenin pathway.Cancer drug resistance (Alhambra, Calif.) · 2025Article
- METTL3 silencing inhibits ferroptosis to suppress ovarian fibrosis in PCOS by upregulating m6A modification of GPX4.Journal of molecular histology · 2024Article
- Transcriptome analysis of the aortic coarctation area.Journal of molecular and cellular cardiology plus · 2024Article
- Monoterpene linalool restrains gentamicin-mediated acute kidney injury in rats by subsiding oxidative stress, apoptosis, and the NF-κB/iNOS/TNF-α/IL-1β pathway and regulating TGF-β.Naunyn-Schmiedeberg's archives of pharmacology · 2024Article
- Deciphering the fibrotic process: mechanism of chronic radiation skin injury fibrosis.Frontiers in immunology · 2024Review
13 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
rationaleEndovascular interventions performed for atherosclerotic lesions trigger excessive vascular smooth muscle cell (SMC) proliferation leading to intimal hyperplasia. Our previous studies show that following endovascular injury, elevated TGF-β/Smad3 promotes SMC proliferation and intimal hyperplasia. Furthermore in cultured SMCs, elevated TGF-β/Smad3 increases the expression of several Wnt genes. Here we investigate a crosstalk between TGF-β/Smad3 and Wnt/β-catenin signaling and its role in SMC proliferation. METHODS AND
resultsTo mimic TGF-β/Smad3 up-regulation in vivo, rat aortic SMCs were treated with Smad3-expressing adenovirus (AdSmad3) or AdGFP control followed by stimulation with TGF-β1 (or solvent). AdSmad3/TGF-β treatment up-regulated Wnt2b, Wnt4, Wnt5a, Wnt9a, and Wnt11 (confirmed by qRT-PCR and ELISA), and also increased β-catenin protein as detected by Western blotting. Blocking Wnt signaling using a Frizzled receptor inhibitor (Niclosamide) abolished TGF-β/Smad3-induced β-catenin stabilization. Increasing β-catenin through degradation inhibition (using SKL2001) or by adenoviral expression enhanced SMC proliferation. Furthermore, application of recombinant Wnt2b, Wnt4, Wnt5a, or Wnt9a, but not Wnt11, stabilized β-catenin and stimulated SMC proliferation as well. In addition, increased β-catenin was found in the neointima of injured rat carotid artery where TGF-β and Smad3 are known to be up-regulated.
conclusionsThese results suggest a novel mechanism whereby elevated TGF-β/Smad3 stimulates the secretion of canonical Wnts which in turn enhances SMC proliferation through β-catenin stabilization. This crosstalk between TGF-β/Smad3 and Wnt/β-catenin canonical pathways provides new insights into the pathophysiology of vascular SMCs linked to intimal hyperplasia.
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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.