Nrf3-Pla2g7 interaction plays an essential role in smooth muscle differentiation from stem cells
Abstract
Objective—: Phospholipase A 2 , group 7 (Pla2g7) is an important mediator in cardiovascular development and diseases because of its divergent physiological and pathological functions in inflammation and oxidative stress. However, little is known about the functional role of Pla2g7 in smooth muscle cell (SMC) differentiation from stem cells. Methods and Results—: In the present study, embryonic stem cells were cultivated on collagen IV-coated plates to allow SMC differentiation. Pla2g7 gene expression and activity were upregulated significantly following 4 to 14 days of cell differentiation and colocalized with SMC differentiation markers in the differentiated SMCs. Knockdown of Pla2g7 resulted in downregulation of smooth muscle–specific markers in vitro and impairment of SMC differentiation in vivo, whereas enforced expression of Pla2g7 enhanced SMC differentiation and increased reactive oxygen species generation. Importantly, enforced expression of Pla2g7 significantly increased the binding of serum response factor to SMC differentiation gene promoters, resulting in SMC differentiation, which was abolished by free radical scavenger and flavoprotein inhibitor of NADPH oxidase but not hydrogen peroxide inhibitor. Moreover, we demonstrated that nuclear factor erythroid 2-related factor 3 (Nrf3) regulates Pla2g7 gene expression through direct binding to the promoter regions of Pla2g7 gene. Conclusion—: Our findings demonstrated that Pla2g7 plays a crucial physiological role in SMC differentiation from stem cells, and the fine interactions between Nrf3 and Pla2g7 are essential for SMC differentiation.
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Nrf3 regulates VSMC differentiation from stem cells via NADPH oxidase-mediated generation of reactive oxygen species.
“Importantly, we have reported that Nrf3 regulates VSMC differentiation from stem cells via NADPH oxidase-mediated generation of reactive oxygen species (ROS).14,15”
From Novel roles of Nrf3–Trim5 axis in vascular smooth muscle cell dysfunctions and neointimal hyperplasia (2025) · cites this paper as [14]
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- Authors
- Xiao, Q., Pepe, A. E., Wang, G., Luo, Z., Zhang, L., Zeng, L., Zhang, Z., Hu, Y., Ye, S., & Xu, Q.
- Affiliations
- Queen Mary University of London (GB)
- ORCID
- Venue
- Arteriosclerosis, Thrombosis, and Vascular Biology
- Published
- 2012-03
- Volume
- 32
- Issue
- 3
- Pages
- 730-744
- ISSN
- 1079-5642 (ISSN-L)
- 1524-4636
- OpenAlex
- W2020499012
- Cited by
- 56
- References
- 66
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 2 · 2023: 4 · 2022: 5 · 2021: 1 · 2020: 1 · 2019: 3 · 2018: 4 · 2017: 7 · 2016: 4 · 2015: 6 · 2014: 4 · 2013: 8 · 2012: 1
- FWCI
- 2.44
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Arteriosclerosis Thrombosis and Vascular Biology (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (King's College London) (submittedVersion)
- Funders
- British Heart Foundation (FS/09/044/28007, PG/11/40/28891, RG/09/004/27647)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics, phytochemicals, and oxidative stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Keywords
- PLA2G7, Nrf3, smooth muscle differentiation, embryonic stem cells, serum response factor, reactive oxygen species, NADPH oxidase, promoter regulation, oxidative stress, cardiovascular development
- MeSH terms
- Animals, Binding Sites, Cell Differentiation, Cell Line, Enzyme Inhibitors, Hydrogen Peroxide, Mice, Inbred C57BL, Phosphorylation, Promoter Regions, Genetic, Protein Binding, Superoxides, Time Factors, Transfection, Biomarkers, Transcriptional Activation, Up-Regulation, Free Radical Scavengers, Gene Expression Regulation, Developmental, Neovascularization, Physiologic, NADPH Oxidases, Serum Response Factor, Serum Response Element, Myocytes, Smooth Muscle, RNA Interference, 1-Alkyl-2-acetylglycerophosphocholine Esterase, Basic-Leucine Zipper Transcription Factors, Mice, Embryonic Stem Cells, Phospholipases A2
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