ArticleAmerican journal of physiology. Heart and circulatory physiology2009
TGF-beta through Smad3 signaling stimulates vascular smooth muscle cell proliferation and neointimal formation.
Article in American journal of physiology. Heart and circulatory physiology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 98 papers.
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Who cites it
98 citing papers in PubMed, 159 citations in OpenAlex.
- Molecular Mechanisms of Intimal Hyperplasia in Saphenous Vein Grafts After Coronary Artery Bypass Grafting.Cells · 2026Review
- Coronary artery disease risk gene PRDM16 regulates smooth muscle homeostasis.Journal of molecular and cellular cardiology · 2026Article
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- Integrative functional genomics analysis identifies pleiotropic genes for vascular diseases.Nature communications · 2026Article
- A prevalent disease-associated SNP in the humanNAR molecular medicine · 2026Article
- Decoding the Kruppel-like Transcription Factors in Atherosclerosis: Insight from Molecular and Translational Perspectives.International journal of molecular sciences · 2025Review
- Microvascular Health as a Key Determinant of Organismal Aging.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Modelling Atherosclerotic Plaque Cap Mechanics: Microcalcifications Reduce Mechanical Properties in Mesenchymal Stromal Cell-Based Model.Advanced biology · 2025Article
- Porphyromonas gingivalis Type 9 Secretion System Promotes Dysregulation of Vascular Smooth Muscle Cell Plasticity With Perturbed TGF-β/Smad Signaling.MicrobiologyOpen · 2025Article
- Elevated Expression ofBiomedicines · 2025Article
- Unveiling cellular and molecular aspects of ascending thoracic aortic aneurysms and dissections.Basic research in cardiology · 2024Review
- Role of collagen and immunostaining for TGF-β in the clinical and microscopic findings of pyogenic granuloma and peripheral ossifying fibroma.Medicina oral, patologia oral y cirugia bucal · 2024Article
- Article
- Transfer RNA-derived small RNA tRF-Glu-CTC attenuates neointimal formation via inhibition of fibromodulin.Cellular & molecular biology letters · 2024Article
- Hypoxia-induced signaling in the cardiovascular system: pathogenesis and therapeutic targets.Signal transduction and targeted therapy · 2023Review
- Review
- FAM3A reshapes VSMC fate specification in abdominal aortic aneurysm by regulating KLF4 ubiquitination.Nature communications · 2023Article
- Impact of the transforming growth factor-β pathway on vascular restenosis and its mechanism.Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2023Article
- Article
- Molecular Characterization of Non-Neurogenic and Neurogenic Lower Urinary Tract Dysfunction (LUTD) in SCI-Induced and Partial Bladder Outlet Obstruction Mouse Models.International journal of molecular sciences · 2023Article
38 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
The objective of this study was to better understand the role of transforming growth factor-beta (TGF-beta) and its primary signaling protein Smad3 in the development of intimal hyperplasia. Male Sprague-Dawley rats underwent left carotid balloon injury followed by intra-arterial infection with adenovirus-expressing Smad3 (AdSmad3). In uninfected injured arteries, endogenous Smad3 was upregulated with the expression peaking at 14 days. Moreover, in arteries infected with AdSmad3, we observed an enhancement of intimal hyperplasia and increased vascular smooth muscle cell (VSMC) proliferation. The novel finding, that TGF-beta/Smad3 stimulated rather than inhibited VSMC proliferation, was confirmed in cultured VSMCs infected with AdSmad3 and treated with TGF-beta. To identify the mechanism underlying TGF-beta/Smad3-mediated VSMC proliferation, we studied the cyclin-dependent kinase inhibitor p27. Although the upregulation of Smad3 in VSMCs had no significant effect on total p27 levels, Smad3 did stimulate the phosphorylation of p27 at serine-10 as well as the nuclear export of p27, events associated with cell proliferation. Furthermore, serine-10-phosphorylated p27 was also increased in AdSmad3-infected injured rat carotid arteries, demonstrating the existence of this same mechanism in vivo. In conclusion, our findings identify a novel mechanism for the effect of TGF-beta on intimal hyperplasia. In the presence of elevated levels of Smad3 that develop in response to injury, TGF-beta stimulates smooth muscle cell proliferation through a mechanism involving the phosphorylation and nuclear export of p27.
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