Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1189176 | ENA |
REPOSITORIES: ENA
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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.
2022-12-14 | GSE216305 | GEO
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.
2022-12-14 | GSE216303 | GEO
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: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.
2020-10-20 | GSE142417 | GEO
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:We applied the transcriptome profiling (RNA-seq) for high-throughput profiling of genes changes in the phenotypic switch of VSMCs. Rat primary VSMCs were divided into 3 groups, control, PDGF-BB, PDGF-BB+PTUPB,and mRNA sequence were performed. We found that Cell cycle related genes and cellular senescence related genes were significantly upregulated by PDGF-BB and significantly reversed by PTUPB. Subsequently, we deleted PTTG1 as a key gene for PTUPB to reverse phenotypic switching in VSMCs. Our study provided the transcription changes by RNA-seq in VSMC phenotypic switch, and found that PTUPB played a crucial role in correcting the dysregulation of sEH/COX-2 derived ARA metabolism in VSMC phenotypic switch
2023-09-01 | GSE241545 | GEO
Project description:Chronic kidney disease (CKD) accelerates vascular calcification (VC) via phenotypic switching of vascular smooth muscle cells (VSMCs). We investigated the roles of circulating small extracellular vesicles (sEVs) between the kidneys and VSMCs and uncovered relevant sEV-propagated microRNAs (miRNAs) and their biological signaling pathways. We established CKD models in rats and mice by adenine-induced tubulointerstitial fibrosis. The miRNA transcriptome of sEVs revealed a depletion of several miRNAs in CKD. Their expression levels in sEVs from CKD patients were correlated to kidney function. This study revealed the transcriptomic landscape of miRNAs propagated in sEVs in CKD. We investigated the therapeutic potential of miRNAs in VC.
2022-12-31 | GSE217558 | GEO
Project description:Atherosclerosis, which develops in the inner layer of arteries, is the major cause of myocardial infarction and stroke. Atherosclerotic plaques develop preferentially in arterial regions exposed to disturbed blood flow, such as vessel curvatures, bifurcations and branching points, where endothelial cells develop an inflammatory phenotype. How disturbed flow induces endothelial cell inflammation is incompletely understood. We show here that histone H3.3 phosphorylation at serine 31 (H3.3S31) plays a critical role in disturbed flow-induced endothelial inflammation, as it allows the rapid induction of FOS and FOSB, which are required for disturbed flow-induced inflammatory gene expression. We identified protein kinase N1 (PKN1) as the kinase responsible for disturbed flow-induced H3.3S31 phosphorylation. PKN1 becomes activated by disturbed flow in an integrin a5b1-dependent manner and then translocates to the cell nucleus. We found that PKN1 is also involved in the phosphorylation of the AP-1 transcription factor JUN. Mice with endothelium-specific loss of PKN1 or endothelial expression of S31 phosphorylation-deficient mutants of H.3.3 show reduced endothelial inflammation and disturbed flow-induced vascular remodeling in vitro and in vivo. Our data identify a novel mechanism of H3.3S31 phosphorylation which may serve as a target for preventive and therapeutic anti-atherosclerotic strategies.
2024-11-26 | GSE261754 | GEO
Project description:Atherosclerosis, which develops in the inner layer of arteries, is the major cause of myocardial infarction and stroke. Atherosclerotic plaques develop preferentially in arterial regions exposed to disturbed blood flow, such as vessel curvatures, bifurcations and branching points, where endothelial cells develop an inflammatory phenotype. How disturbed flow induces endothelial cell inflammation is incompletely understood. We show here that histone H3.3 phosphorylation at serine 31 (H3.3S31) plays a critical role in disturbed flow-induced endothelial inflammation, as it allows the rapid induction of FOS and FOSB, which are required for disturbed flow-induced inflammatory gene expression. We identified protein kinase N1 (PKN1) as the kinase responsible for disturbed flow-induced H3.3S31 phosphorylation. PKN1 becomes activated by disturbed flow in an integrin a5b1-dependent manner and then translocates to the cell nucleus. We found that PKN1 is also involved in the phosphorylation of the AP-1 transcription factor JUN. Mice with endothelium-specific loss of PKN1 or endothelial expression of S31 phosphorylation-deficient mutants of H.3.3 show reduced endothelial inflammation and disturbed flow-induced vascular remodeling in vitro and in vivo. Our data identify a novel mechanism of H3.3S31 phosphorylation which may serve as a target for preventive and therapeutic anti-atherosclerotic strategies.
2024-11-26 | GSE261755 | GEO