Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

GLS1 governs vascular smooth muscle cell phenotypic switching and aortic dissection via glutamate metabolism

ABSTRACT: To evaluate the roles of glutaminase 1 (GLS1) in vascular smooth muscle cells (VSMCs) phenotypic switching and aortic dissection (AD). Integrative transcriptomic analyses were performed to identify the candidate genes involved in VSMC phenotypic switching in AD. The expression of GLS1 in VSMCs was assessed by qRT-PCR, Western blot and immunofluorescence. RNA-sequencing analysis was performed to recapitulate possible changes in the transcriptome profile of GLS1 in VSMCs. We identified GLS1 as a potential regulator in AD. GLS1 expression was significantly downregulated in VSMCs from both human AD aortic tissues and mouse models. Mechanistically, down-regulation of GLS1 impaired glutamate metabolism, leading to reduced levels of glutathione and α-ketoglutarate, thereby promoting mitochondrial dysfunction and accumulation of reactive oxygen species, which activated the PI3K/AKT pathway and ultimately triggered VSMC phenotypic switching. These findings revealed a critical role of GLS1-mediated glutamate metabolism in VSMC phenotypic switching and suggest a promising therapeutic target for AD.

ORGANISM(S): Homo sapiens

PROVIDER: GSE324926 | GEO | 2026/03/20

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other
	GSE324926_genes_fpkm_expression.xlsx	Xlsx

Items per page:

1 - 2 of 2

Similar Datasets

Interleukin-11 signaling drives vascular smooth muscle phenotypic switching and contributes to aortic remodelling

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

GLS1 interactome in liver cells by IP followed by LC-MS/MS

Project description:Glutaminase (GLS1) is involved in the development of Alcoholic liver disease (ALD). Protein-protein interactions underlie the biological processes impacted by GLS1. we used immunoprecipitation-mass spectrometry (IP-MS) technology and found the proteins interacted with GLS1.

2025-12-08 | PXD050603 | Pride

Microvascular smooth muscle cells exhibit divergent phenotypic switching responses to platelet-derived growth factor and insulin-like growth factor 1

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.

2025-12-09 | GSE312686 | GEO

Disfunction of arachidonic acid metabolism in vascular smooth muscle cells contributes to restenosis

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

CTHRC1 is a new therapeutic target and serum diagnostic biomarker for aortic dissection [Ab_mouse_RNAseq]

Project description:Aortic dissection (AD) is a cardiovascular disease with rapid onset and extremely high short-term mortality, currently lacking specific peripheral blood-based biomarkers and effective treatments. Here, our analyses of AD samples from animal models and human patients revealed elevated blood levels of CTHRC1, a protein secreted by vascular fibroblasts. Furthermore, CTHRC1 regulates the phenotypic switch of vascular smooth muscle cells (VSMCs) during arterial remodeling by binding to ADAM9 on the VSMC membrane, activating the ERK1/2 signaling pathway, and promoting a contractile-to-synthetic transition. In Ang-II/BAPN induced AD mouse models, genetic ablation or antibody-mediated blockade of CTHRC1 effectively prevented AD formation and development. These findings unveil activated vascular fibroblast derived CTHRC1 as a critical regulator of VSMC phenotype and aortic structural integrity via the ERK1/2 signaling pathway, suggesting its potential as a novel serum diagnostic biomarker for AD diagnostic and a promising therapeutic target. Collectively, our data propose a new and effective strategy for diagnosis and clinical management of patients with AD.

2025-08-19 | GSE297520 | GEO

CTHRC1 is a new therapeutic target and serum diagnostic biomarker for aortic dissection [MOVAS_rhCTHRC1_RNAseq]

2025-08-19 | GSE297519 | GEO

CTHRC1 is a new therapeutic target and serum diagnostic biomarker for aortic dissection [Cthrc1_wt_ko_RNAseq]

2025-08-19 | GSE297518 | GEO

Thymosin 4 protects against aortic aneurysm via endocytic regulation of growth factor signalling

Project description:Vascular stability and tone are maintained by contractile smooth muscle cells (VSMCs). However, injury-induced growth factors stimulate a contractile-synthetic phenotypic modulation which increases susceptibility to abdominal aortic aneurysm (AAA). As a regulator of embryonic VSMC differentiation, we hypothesised that Thymosin β4 (Tβ4) may function to maintain healthy vasculature throughout postnatal life. This was supported by the identification of an interaction with Low density lipoprotein receptor related protein 1 (LRP1), an endocytic regulator of PDGF-BB signalling and VSMC proliferation. LRP1 variants have been implicated by genome-wide association studies with risk of AAA and other arterial diseases. T4-null mice displayed aortic VSMC and elastin defects, phenocopying LRP1 mutants, and their compromised vascular integrity predisposed to Angiotensin II-induced aneurysm formation. Aneurysmal vessels were characterised by enhanced VSMC phenotypic modulation and augmented platelet-derived growth factor (PDGF) receptor (PDGFR)β signalling. In vitro, enhanced sensitivity to PDGF-BB, upon loss of Tβ4, associated with dysregulated endocytosis, with increased recycling and reduced lysosomal targeting of LRP1-PDGFRβ. Accordingly, the exacerbated aneurysmal phenotype in T4-null mice was rescued upon treatment with the PDGFRβ antagonist, Imatinib. Our study identifies Tβ4 as a key regulator of LRP1 for maintaining vascular health and provides insights into the mechanisms of growth factor-controlled VSMC phenotypic modulation underlying aortic disease progression.

2021-05-21 | PXD024162 | Pride

Spatial Proteomics Profiling of Vascular Smooth Muscle Cells and Atherosclerotic Plaques in a Diabetic Atherosclerosis Mouse Model

Project description:This project presents a spatial proteomic investigation of vascular smooth muscle cells (VSMCs) and atherosclerotic plaque regions in a diabetic mouse model of atherosclerosis (DMAS). Using ApoE-/- mice fed with a high-fat diet and treated with low-dose streptozotocin (STZ) to induce a diabetic phenotype, we performed laser capture microdissection (LCM) to separately isolate plaque regions and adjacent VSMC-rich areas of the aortic arch. Subsequently, spatially resolved proteomic profiling was carried out using LC-MS/MS, followed by quantitative analysis based on iBAQ values. Differentially expressed proteins between plaque and VSMC regions were identified and enriched pathway analysis revealed significant alterations in oxidative stress response, insulin signaling, mitochondrial function, RNA transport, and extracellular matrix remodeling under diabetic conditions. Of particular interest, the spatial proteomics data highlighted a marked downregulation of the nuclear pore complex protein Nup93 in VSMCs from diabetic mice, implicating impaired nuclear transport and dysregulation of RNA alternative splicing. This finding was supported by transcriptomic integration and functional analyses that revealed aberrant splicing of SerpinE2, a gene associated with cell proliferation and ECM accumulation. This dataset provides region-specific, high-resolution proteomic profiles of vascular tissues in a diabetic atherosclerosis model. It serves as a valuable resource for investigating the spatial heterogeneity of vascular pathology and the molecular mechanisms underlying diabetes-accelerated atherosclerosis. The raw and processed data can be used to explore protein expression dynamics, identify spatiotemporal biomarkers, and validate candidate targets such as Nup93 and SerpinE2 involved in VSMC phenotypic switching.

2025-09-29 | PXD063231 | Pride

Single-nucleus RNA sequencing of the prefrontal cortex from mice lacking glutaminase 1 in CamKIIa-positive neurons and control mice

Project description:Autism spectrum disorder (ASD) is a heterogeneous group of disorders with shared diagnostic phenotypes, such as reduced interest in social interaction and communication, and increased stereotyped or restricted interests and behaviors. Little is known about the involvement of alterations of glutaminase 1 (Gls1, an enzyme that catalyzes the hydrolysis of glutamine into glutamate) in the pathogenesis of ASD. To investigate the role of Gls1 in forebrain neurons , we generated conditional mouse mutants with loss of Gls1 in forebrain CamKIIα-Cre positive neurons by crossing Gls1flox/flox mice with CamKIIαcre mice.

2023-05-31 | GSE233639 | GEO