Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1189176 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR31439120_1.fastq.gz | Fastqsanger.gz | |||
| SRR31439120_2.fastq.gz | Fastqsanger.gz |
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Project description:Vascular smooth muscle cells (VSMCs) within atherosclerotic lesions undergo a phenotypic switching in a KLF4-dependent manner. Glycolysis plays important roles in transdifferentiation of somatic cells, however, it is unclear whether and how KLF4 mediates the link between glycolytic switch and VSMCs phenotypic transitions. Here, we show that KLF4 upregulation accompanies VSMCs phenotypic switching in atherosclerotic lesions. KLF4 enhances the metabolic switch to glycolysis through increasing PFKFB3 expression. Inhibiting glycolysis suppresses KLF4-induced VSMCs phenotypic switching, demonstrating that glycolytic shift is required for VSMCs phenotypic switching. Mechanistically, KLF4 upregulates expression of circCTDP1 and eEF1A2, both of which cooperatively promote PFKFB3 expression. TMAO induces glycolytic shift and VSMCs phenotypic switching by upregulating KLF4. Our study indicates that KLF4 mediates the link between glycolytic switch and VSMCs phenotypic transitions, suggesting that a previously unrecognized KLF4-eEF1A2/circCTDP1-PFKFB3 axis plays crucial roles in VSMCs phenotypic switching.
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Project description:Vascular smooth muscle cells (VSMCs) within atherosclerotic lesions undergo a phenotypic switching in a KLF4-dependent manner. Glycolysis plays important roles in transdifferentiation of somatic cells, however, it is unclear whether and how KLF4 mediates the link between glycolytic switch and VSMCs phenotypic transitions. Here, we show that KLF4 upregulation accompanies VSMCs phenotypic switching in atherosclerotic lesions. KLF4 enhances the metabolic switch to glycolysis through increasing PFKFB3 expression. Inhibiting glycolysis suppresses KLF4-induced VSMCs phenotypic switching, demonstrating that glycolytic shift is required for VSMCs phenotypic switching. Mechanistically, KLF4 upregulates expression of circCTDP1 and eEF1A2, both of which cooperatively promote PFKFB3 expression. TMAO induces glycolytic shift and VSMCs phenotypic switching by upregulating KLF4. Our study indicates that KLF4 mediates the link between glycolytic switch and VSMCs phenotypic transitions, suggesting that a previously unrecognized KLF4-eEF1A2/circCTDP1-PFKFB3 axis plays crucial roles in VSMCs phenotypic switching.
2022-11-09 | PXD038057 |
Project description:Vascular smooth muscle cells (VSMCs) within atherosclerotic lesions undergo a phenotypic switching in a KLF4-dependent manner. Glycolysis plays important roles in transdifferentiation of somatic cells, however, it is unclear whether and how KLF4 mediates the link between glycolytic switch and VSMCs phenotypic transitions. Here, we show that KLF4 upregulation accompanies VSMCs phenotypic switching in atherosclerotic lesions. KLF4 enhances the metabolic switch to glycolysis through increasing PFKFB3 expression. Inhibiting glycolysis suppresses KLF4-induced VSMCs phenotypic switching, demonstrating that glycolytic shift is required for VSMCs phenotypic switching. Mechanistically, KLF4 upregulates expression of circCTDP1 and eEF1A2, both of which cooperatively promote PFKFB3 expression. TMAO induces glycolytic shift and VSMCs phenotypic switching by upregulating KLF4. Our study indicates that KLF4 mediates the link between glycolytic switch and VSMCs phenotypic transitions, suggesting that a previously unrecognized KLF4-eEF1A2/circCTDP1-PFKFB3 axis plays crucial roles in VSMCs phenotypic switching.
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Project description:RNA sequencing of primary human aortic or arterial VSMCs after stimulation with transforming growth factor beta-1 (TGFβ1) revealed marked IL11 upregulation. In vitro, IL11 stimulation of VSMCs resulted in phenotypic switching by increased ECM production and migration/invasion. Neutralizing IL11 antibody treatment abolished phenotypic switching in VSMCs. IL11 plays an important and non-redundant role in VSMC phenotypic switching.
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Project description:Objective: Vascular smooth muscle cell (VSMC) phenotypic switching is critical for normal vessel formation, vascular stability, and healthy brain aging. Phenotypic switching is regulated by mediators including platelet derived growth factor (PDGF)-BB, insulin-like growth factor (IGF-1), as well as transforming growth factor-β (TGF-β) and endothelin-1 (ET-1), but much about the role of these factors in microvascular VSMCs remains unclear. Methods: We used primary rat microvascular VSMCs to explore PDGF-BB- and IGF-1-induced phenotypic switching. Results: PDGF-BB induced an early proliferative response, followed by formation of polarized leader cells and rapid, directionally coordinated migration. In contrast, IGF-1 induced cell hypertrophy, and only a small degree of migration by unpolarized cells. TGF-β and ET-1 selectively inhibit PDGF-BB-induced VSMC migration primarily by repressing migratory polarization and formation of leader cells. Contractile genes were downregulated by both growth factors, while other genes were differentially regulated by PDGF-BB and IGF-1. Conclusions: These studies indicate that PDGF-BB and IGF-1 stimulate different types of microvascular VSMC phenotypic switching characterized by different modes of cell migration. Our studies are consistent with a chronic vasoprotective role for IGF-1 in VSMCs in the microvasculature while PDGF is more involved in VSMC proliferation and migration in response to acute activities such as neovascularization. Better understanding of the nuances of the phenotypic switching induced by these growth factors is important for our understanding of a variety of microvascular diseases.
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Project description:To comprehensively understand the mechanism by which MYPT1 modulates the phenotypic switching of VSMCs after ischemic stroke, the proteins of cortical small vessel from MYPT1SMKO and WT mice subjected to MCAO or sham group were collected for proteomic screening.
2021-08-21 | PXD027869 | Pride
Project description:BACKGROUND: The phenotypic switching of vascular smooth muscle cells (VSMCs) plays a crucial role in vascular homeostasis. Protein-protein interactions (PPIs) mediated by PDZ domains is essential for cardiac functions. However, little is known about the role of PDZ proteins in regulating the phenotypic switching of VSMCs. In this study, we aim to explore the role of TAX1BP3, a singular PDZ protein, in maintaining the contractile phenotype of VSMCs. METHODS: Subcellular localization of TAX1BP3 was assessed in isolated VSMCs and arteries from mice or donors with in-stent restenosis and atherosclerosis. VSMC-specific Tax1bp3 knockout mice were generated to determine the relevant phenotypes in a carotid artery wire injury model. RNA sequencing, ATAC-sequencing, computational prediction of complex structures, and coCo-immunoprecipitation (Co-IP) were performed to elucidate the underlying molecular mechanisms. AAV-mediated Tax1bp3 gene delivery and recombinant TAX1BP3 were employed to investigate the potential translational relevance. RESULTS: TAX1BP3 exhibited dynamic nucleocytoplasmic shuttling during phenotypic switching of VSMCs. Deficiency of TAX1BP3 facilitated the transition from a contractile to a synthetic phenotype and aggravated neointima formation following vascular injury in mice. The integration of RNA sequencing and ATAC sequencing unveiled that TAX1BP3 primarily regulated the cell cycle progression and cell proliferation of VAMCs through YAP-TEAD transcription activity. The computational prediction of TAX1BP3/YAP1 complex structures and protein interaction related experiments revealed TAX1BP3 and TEAD1 compete for binding to YAP through its TEAD binding domain via a non-canonical PDZ manner. AAV-mediated Tax1bp3 gene delivery markedly attenuated post-injury neointima formation and the progression of atherosclerosis. Recombinant TAX1BP3 administration effectively reduced VSMCs proliferation and intimal hyperplasia following vascular injury in vitro and in vivo. CONCLUSIONS: Our results identified TAX1BP3 , a novel nucleocytoplasmic protein, a singular PDZ protein, that competitively interacts with YAP/-TEAD complex in a non-canonical PDZ manner and exerted its protective role in phenotypic switching and vascular intimal hyperplasia primarily through the regulation of cell proliferation.
2025-09-16 | GSE255239 | GEO
Project description:BACKGROUND: The phenotypic switching of vascular smooth muscle cells (VSMCs) plays a crucial role in vascular homeostasis. Protein-protein interactions (PPIs) mediated by PDZ domains is essential for cardiac functions. However, little is known about the role of PDZ proteins in regulating the phenotypic switching of VSMCs. In this study, we aim to explore the role of TAX1BP3, a singular PDZ protein, in maintaining the contractile phenotype of VSMCs. METHODS: Subcellular localization of TAX1BP3 was assessed in isolated VSMCs and arteries from mice or donors with in-stent restenosis and atherosclerosis. VSMC-specific Tax1bp3 knockout mice were generated to determine the relevant phenotypes in a carotid artery wire injury model. RNA sequencing, ATAC-sequencing, computational prediction of complex structures, and coCo-immunoprecipitation (Co-IP) were performed to elucidate the underlying molecular mechanisms. AAV-mediated Tax1bp3 gene delivery and recombinant TAX1BP3 were employed to investigate the potential translational relevance. RESULTS: TAX1BP3 exhibited dynamic nucleocytoplasmic shuttling during phenotypic switching of VSMCs. Deficiency of TAX1BP3 facilitated the transition from a contractile to a synthetic phenotype and aggravated neointima formation following vascular injury in mice. The integration of RNA sequencing and ATAC sequencing unveiled that TAX1BP3 primarily regulated the cell cycle progression and cell proliferation of VAMCs through YAP-TEAD transcription activity. The computational prediction of TAX1BP3/YAP1 complex structures and protein interaction related experiments revealed TAX1BP3 and TEAD1 compete for binding to YAP through its TEAD binding domain via a non-canonical PDZ manner. AAV-mediated Tax1bp3 gene delivery markedly attenuated post-injury neointima formation and the progression of atherosclerosis. Recombinant TAX1BP3 administration effectively reduced VSMCs proliferation and intimal hyperplasia following vascular injury in vitro and in vivo. CONCLUSIONS: Our results identified TAX1BP3 , a novel nucleocytoplasmic protein, a singular PDZ protein, that competitively interacts with YAP/-TEAD complex in a non-canonical PDZ manner and exerted its protective role in phenotypic switching and vascular intimal hyperplasia primarily through the regulation of cell proliferation.
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