Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Endothelial cell senescence exacerbates pulmonary hypertension by inducing juxtacrine Notch signaling in smooth muscle cells

ABSTRACT: Endothelial cell senescence exacerbates pulmonary hypertension by inducing juxtacrine Notch signaling in smooth muscle cells

PROVIDER: PRJNA950045 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR24006371_1.fastq.gz	Fastqsanger.gz
	SRR24006371_2.fastq.gz	Fastqsanger.gz
	SRR24006372_1.fastq.gz	Fastqsanger.gz
	SRR24006372_2.fastq.gz	Fastqsanger.gz
	SRR24006373_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 8

Similar Datasets

Endothelial cell senescence exacerbates pulmonary hypertension by inducing juxtacrine Notch signaling in smooth muscle cells

Project description:Pulmonary arterial hypertension (PAH) is a fatal disease characterized by a progressive increase in pulmonary artery pressure caused by pathological pulmonary artery remodeling. Here, we show that endothelial cell (EC) senescence plays a negative role in pulmonary hypertension via juxtacrine interaction with smooth muscle cells (SMCs). By using EC-specific progeroid mice that we recently generated, we discovered that EC progeria deteriorated vascular remodeling in the lungs, and exacerbated pulmonary hypertension in mice exposed to chronic hypoxia. Mechanistically, senescent ECs overexpressed Notch ligands, which resulted in increased Notch signaling and activated proliferation and migration capacities in neighboring SMCs. Pharmacological inhibition of Notch signaling reduced the effects of senescent ECs on SMCs functions in vitro, and improved the worsened pulmonary hypertension in EC-specific progeroid mice in vivo. Our findings show that EC senescence is a critical disease-modifying factor in PAH and that EC-mediated Notch signaling is a pharmacotherapeutic target for the treatment of PAH, particularly in the elderly.

2023-04-30 | GSE228491 | GEO

Endothelial cell senescence exacerbates pulmonary hypertension by inducing juxtacrine Notch signaling in smooth muscle cells.

Project description:Pulmonary arterial hypertension (PAH) is a fatal disease characterized by a progressive increase in pulmonary artery pressure caused by pathological pulmonary artery remodeling. Here, we demonstrate that endothelial cell (EC) senescence plays a negative role in pulmonary hypertension via juxtacrine interaction with smooth muscle cells (SMCs). By using EC-specific progeroid mice, we discovered that EC progeria deteriorated vascular remodeling in the lungs, and exacerbated pulmonary hypertension in mice. Mechanistically, senescent ECs overexpressed Notch ligands, which resulted in increased Notch signaling and activated proliferation and migration capacities in neighboring SMCs. Pharmacological inhibition of Notch signaling reduced the effects of senescent ECs on SMCs functions in vitro, and improved the worsened pulmonary hypertension in EC-specific progeroid mice in vivo. Our findings show that EC senescence is a critical disease-modifying factor in PAH and that EC-mediated Notch signaling is a pharmacotherapeutic target for the treatment of PAH, particularly in the elderly.

| S-EPMC10182325 | biostudies-literature

DNA methylation signatures of pulmonary arterial smooth muscle cells in chronic thromboembolic pulmonary hypertension

Project description:DNA methylation signatures of pulmonary arterial smooth muscle cells in chronic thromboembolic pulmonary hypertension

2018-04-13 | GSE113061 | GEO

RNA sequencing of healthy and diseased (idiopathic pulmonary hypertension) human pulmonary artery smooth muscle cells

Project description:We performed RNA-seq to analyze gene expression in human PASMCs (Pulmonary arterial smooth muscle cells) isolated from subjects without disease and from subjects with IPAH (idiopathic pulmonary hypertension)

2020-07-15 | GSE144274 | GEO

Hypertension reduces soluble guanylyl cyclase expression in the mouse aorta via the Notch signaling pathway

Project description:Hypertension is a dominating risk factor for cardiovascular disease. To characterize the genomic response to hypertension, we administered vehicle or angiotensin II to mice and performed gene expression analyses. AngII treatment resulted in a robust increase in blood pressure and altered expression of 235 genes in the aorta, including Gucy1a3 and Gucy1b3 which encode subunits of soluble guanylyl cyclase (sGC). Western blotting and immunohistochemistry confirmed repression of sGC associated with curtailed relaxation via sGC activation. Analysis of transcription factor binding motifs in promoters of differentially expressed genes identified enrichment of motifs for RBPJ, a component of the Notch signaling pathway, and the Notch coactivators FRYL and MAML2 were reduced. Gain and loss of function experiments demonstrated that JAG/NOTCH signaling controls sGC expression together with MAML2 and FRYL. Reduced expression of sGC, correlating with differential expression of MAML2 in stroke prone and spontaneously hypertensive rats was also seen and RNA-Seq data demonstrated correlations between JAG1, NOTCH3, MAML2 and FRYL and the sGC subunits GUCY1A3 and GUCY1B3 in human coronary artery. Notch signaling thus provides a constitutive drive on expression of the major nitric oxide receptor (GUCY1A3/GUCY1B3) in arteries from mice, rats, and humans, and this control mechanism is disturbed in hypertension.

2017-05-01 | GSE93597 | GEO

Parathyroid hormone exacerbates pulmonary hypertension through hypoxia-induced parathyroid hormone receptor upregulation.

Project description:Parathyroid hormone exacerbates pulmonary hypertension through hypoxia-induced parathyroid hormone receptor upregulation.

| PRJNA1025021 | ENA

Sirt6 Deficiency Exacerbates Podocyte Injury and Proteinuria through Targeting Notch Signaling

Project description:Podocyte injury is a major determinant in proteinuric kidney disease and identification of potential therapeutic targets for preventing podocyte injury has clinical importance. Here, we show that histone deacetylase Sirt6 protects against podocyte injury through epigenetic regulation of Notch signaling. Sirt6 is downregulated in renal biopsies from patients with podocytopathies and its expression negatively correlates withglomerular filtration rate. Podocyte-specific deletion of Sirt6 exacerbates podocyte injury and proteinuria in two independent mouse models including diabetic nephropathy and adriamycin-induced nephropathy. Sirt6 has pleiotropic protective actions in podocytes including anti-inflammatory and anti-apoptotic effects, is involved in actin cytoskeleton maintenance, and promotes autophagy. Sirt6 also reduces urokinase plasminogen activator receptor expression, which is a key factor for podocyte foot process effacement and proteinuria. Mechanistically, Sirt6 inhibits Notch1 and Notch4 transcription by deacetylating the histone H3K9. We suggest Sirt6 as a potential therapeutic target in proteinuric kidney disease.

2017-06-20 | GSE100185 | GEO

Loss of hepatic DRP1 exacerbates alcoholic hepatitis by inducing megamitochondria and mitochondrial maladaptation

Project description:Loss of hepatic DRP1 exacerbates alcoholic hepatitis by inducing megamitochondria and mitochondrial maladaptation

| PRJNA853551 | ENA

Angiogenesis gene expression upon Notch activation in human vascular smooth muscle cells

Project description:VSMCs were cultured on Jag1 or IgG-coated plates as described above. RNA was extracted using RNA isolation kit (Qiagen). Reverse-transcription PCR was done with RNA-to-cDNA kit (Applied Biosystems). cDNA was run on a TaqMan Low-Density Array, human angiogenesis panel (Applied Biosystems , Cat#4378725), amplified on a 7900 HT Fast Real Time PCR system (Applied Biosystems) according to manufacturer’s instructions. Angiogenesis gene expression was screened for human aortic vascular smooth muscle cells that were plated for 18 hours on either Notch ligands (Jag1 or Jag2) as compared to appropriate IgG controls (IgG1 or IgG2).

2011-12-01 | E-GEOD-34024 | biostudies-arrayexpress

microRNA expression profile in vascular smooth muscle cells (VSMCs) after inducing calcification

Project description:microRNA expression profile in vascular smooth muscle cells (VSMCs) after inducing calcification

| PRJNA540465 | ENA