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Nox5 mediates PDGF-induced proliferation in human aortic smooth muscle cells
Open accessAbstract
The proliferation of vascular smooth muscle cells is important in the pathogenesis of many vascular diseases. Reactive oxygen species (ROS) produced by NADPH oxidases in smooth muscle cells have been shown to participate in signaling cascades regulating proliferation induced by platelet-derived growth factor (PDGF), a powerful smooth muscle mitogen. We sought to determine the role of Nox5 in the regulation of PDGF-stimulated human aortic smooth muscle cell (HASMC) proliferation. Cultured HASMC were found to express four isoforms of Nox5. When HASMC stimulated with PDGF were pretreated with N-acetyl cysteine (NAC), proliferation was significantly reduced. Proliferation induced by PDGF was also heavily dependent on JAK/STAT activation, as the JAK inhibitor, AG490, was able to completely abolish PDGF-stimulated HASMC growth. Specific knockdown of Nox5 with a siRNA strategy reduced PDGF-induced HASMC ROS production and proliferation. Additionally, siRNA to Nox5 inhibited PDGF-stimulated JAK2 and STAT3 phosphorylation. ROS produced by Nox5 play an important role in PDGF-induced JAK/STAT activation and HASMC proliferation.
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“As indicated above, the particular architecture of NOX5 indicates a regulation of its activity through Ca2+ levels (62, 469).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [469]
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“In human blood vessels, NOX5 is expressed in ECs and VSMCs (81, 469) (FIGURE 9, Table 5).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [469]
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Metadata
- Authors
- Jay, D. B., Papaharalambus, C. A., Seidel-Rogol, B., Dikalova, A. E., Lassègue, B., & Griendling, K. K.
- Affiliations
- Emory University (US)
- Corresponding author
- Griendling, Kathy K.
- Venue
- Free Radical Biology and Medicine
- Publisher
- Elsevier BV
- Published
- 2008-08
- Volume
- 45
- Issue
- 3
- Pages
- 329-335
- ISSN
- 0891-5849 (ISSN-L)
- PMC
- PMC2459308
- OpenAlex
- W2049535510
- Cited by
- 166
- References
- 38
- Citations by year
- 2026: 1 · 2024: 4 · 2023: 4 · 2022: 9 · 2021: 3 · 2020: 6 · 2019: 9 · 2018: 12 · 2017: 8 · 2016: 2 · 2015: 12 · 2014: 15 · 2013: 18 · 2012: 18
- FWCI
- 10.16
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Free Radical Biology and Medicine (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Heart, Lung, and Blood Institute (HL058863, F32HL074604, HL074604, R01HL058863)
- Topics
- Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Keywords
- NADPH oxidase 5, platelet-derived growth factor, smooth muscle cell proliferation, human aortic smooth muscle cells, reactive oxygen species, NADPH oxidase, JAK/STAT signaling, JAK2 phosphorylation, STAT3 phosphorylation, N-acetylcysteine, siRNA knockdown, vascular smooth muscle
- MeSH terms
- NADPH Oxidase 5, Aorta, Cells, Cultured, Enzyme Inhibitors, Humans, Membrane Proteins, Muscle, Smooth, Vascular, Phosphorylation, Platelet-Derived Growth Factor, Transfection, Blotting, Western, Reactive Oxygen Species, NADPH Oxidases, Protein Isoforms, Myocytes, Smooth Muscle, Cell Proliferation, STAT3 Transcription Factor, Janus Kinase 2
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