Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Lung selective gene responses to alveolar hypoxia

ABSTRACT: Pulmonary hypoxia is a common complication of chronic lung diseases leading to the development of pulmonary hypertension. The underlying sustained increase in vascular resistance in hypoxia is a response unique to the lung. Thus, we hypothesised that there are genes whose expression is altered selectively in the lung in response to alveolar hypoxia. Using a novel subtractive array strategy, we compared gene responses to hypoxia in primary human pulmonary microvascular endothelial cells to those in cardiac microvascular endothelium and identified genes selectively differentially regulated in the lung endothelium. Keywords: Time course, cell type comparison

ORGANISM(S): Homo sapiens

PROVIDER: GSE11341 | GEO | 2008/11/21

SECONDARY ACCESSION(S): PRJNA106551

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Transcriptomics and proteomics revealed sex differences in human pulmonary microvascular endothelial cells

Project description:There is marked sexual dimorphism displayed in the onset and progression of pulmonary hypertension (PH). Females more commonly develop pulmonary arterial hypertension (PAH), however, females with PAH and other types of PH have better survival than males. Pulmonary microvascular endothelial cells play a crucial role in the pulmonary vascular remodelling and increased pulmonary vascular resistance of PH. Given this background, we hypothesized that there are sex differences in the pulmonary microvascular endothelium basally and in response to hypoxia that are independent of the sex hormone environment.

2024-01-03 | PXD046787 | Pride

Physiological shear stress markedly alters the proteomic response to hypoxia in human pulmonary microvascular endothelial cells

Project description:Physiological shear stress, produced by blood flow, homeostatically regulates the phenotype of pulmonary endothelial cells exerting anti-inflammatory and anti-thrombotic actions and maintaining normal barrier function. In the pulmonary circulation hypoxia, due to high altitude or diseases such as COPD, causes vasoconstriction, increased vascular resistance and pulmonary hypertension. Hypoxia-induced changes in endothelial function play a central role in the development of this pulmonary hypertension. However, the direct interactive effects of hypoxia and shear stress on the pulmonary endothelial phenotype have not been extensively studied. We cultured human pulmonary microvascular endothelial cells (HPMEC) in normoxia or hypoxia while subjected to physiological shear stress or in static conditions. Unbiased proteomics was used to identify hypoxia-induced changes in protein expression. Using publicly available single cell RNA-seq datasets, differences in gene expression between the alveolar endothelial cells from COPD and healthy lungs were identified. 60 proteins were identified in HPMEC lysates whose expression changed in response to hypoxia in sheared but not in static conditions. mRNA for five of these (ERG, MCRIP1, EIF4A2, HSP90AA1 and DNAJA1) showed similar changes in the endothelial cells of COPD compared to healthy lungs. These data show that the proteomic responses of the pulmonary microvascular endothelium to hypoxia are significantly altered by shear stress and suggest that these differences are important in the development of hypoxic pulmonary vascular disease.

2023-02-17 | PXD036260 | Pride

Analysis of Differentially Regulated Genes in Lung Microvasculature

Project description:Pulmonary arterial hypertension (PAH) is a progressive fatal disease that is characterized by pathological pulmonary artery remodeling, in which endothelial cell (EC) dysfunction is critically involved. We herein describe a previously unknown role of endothelial angiocrine in pulmonary hypertension. By searching for genes highly expressed in lung microvascular ECs, we identified inhibin--A (INHBA) as an angiocrine factor produced by pulmonary capillaries. We found that excess production of INHBA by ECs impairs the endothelial function in an autocrine manner by functioning as activin A (ActA). Mechanistically, ActA induces bone morphogenetic protein receptor type 2 (BMPRII) internalization and targeting to lysosomes for degradation, resulting in BMPRII signal deficiency in ECs. When endothelial ActA-BMPRII link is overdriven in mice, hypoxia-induced pulmonary hypertension was exacerbated, whereas conditional knockout of INHBA in ECs prevents the progression of pulmonary hypertension. These data collectively indicate a critical role for the dysregulated endothelial ActA-BMPRII link in the progression of pulmonary hypertension, and thus endothelial INHBA/ActA is an attractive pharmacotherapeutic target for the treatment of PAH.

2020-12-15 | GSE156225 | GEO

Analysis of Differentially Regulated Genes in Lung Tissue

2020-12-15 | GSE156233 | GEO

Reverse Remodelling of the Lung Vasculature after Hypoxia

Project description:Pulmonary hypertension (PH) is a life-threatening disease, characterized by excessive pulmonary vascular remodeling, leading to elevated pulmonary arterial pressure and right heart hypertrophy. PH is caused, among other factors, by chronic hypoxia, leading to hyper-proliferation of pulmonary arterial smooth muscle cells (PASMC) and apoptosis-resistant pulmonary microvascular endothelial cells (PMVEC). Upon re-exposure to normoxia, chronic hypoxia-induced PH in mice is reversible. In this study, we aim to identify novel candidate genes involved in pulmonary vascular remodeling specifically in the pulmonary vasculature.

2022-09-01 | GSE183908 | GEO

E2F1 mediates SOX17 Deficiency-Induced Pulmonary Hypertension

Project description:SRY-Box Transcription Factor 17 (SOX17) enhancers variants and mutations are found in patients with pulmonary arterial hypertension (PAH). In human PAH pulmonary microvascular endothelial cells (HPMVEC), there is a significant downregulation of SOX17 expression. We hypothesized that SOX17 deficiency contributes to the pathogenesis of PAH and found that mice with endothelial specific disruption (ecKO Sox17) developed spontaneous pulmonary hypertension (PH) and exacerbated hypoxia-induced PH. Loss of SOX17 in lung ECs induces cell cycle programming, proliferative and anti-apoptotic phenotypes, a process mediated by the activation of E2F Transcription Factor 1 (E2F1) signaling. Pharmacological inhibition of E2F1 in ecKO Sox17 mice attenuated PH and cell cycle programming. Our study demonstrated that endothelial SOX17 deficiency induces PH and targeting E2F1 signaling represents a promising approach in PAH patients.

2023-03-15 | GSE192649 | GEO

Investigating the expression signatures of circRNA in pulmonary arteial hypertension

Project description:To investigate the underlying mechanism of pulmonary hypertension, the model of hypoxia-treated pulmonary arterial hypertension (PAH) rats were constructed to detect the differentially expressed profile of circRNAs in lung tissue of PAH rat. The whole genome microarray expression profiling analysis as a discovery platform have been employed to identify genes difference.

2023-09-12 | GSE226952 | GEO

Endothelial senescence mediates hypoxia-induced vascular remodeling by modulating PDGFB expression

Project description:Uncontrolled accumulation of pulmonary artery smooth muscle cells (PASMC) to the distal pulmonary arterioles (PAs) is one of the major characteristics of pulmonary hypertension (PH). Cellular senescence contributes to aging and lung diseases associated with PH and links to PH progression. However, the mechanism by which cellular senescence controls vascular remodeling in PH is not fully understood. The levels of senescence marker, p16INK4A and senescence-associated β-galactosidase (SA-β-gal) activity are higher in PA endothelial cells (ECs) isolated from idiopathic pulmonary arterial hypertension (IPAH) patients compared to those from healthy individuals. Hypoxia-induced accumulation of α-smooth muscle actin (αSMA)-positive cells to the PAs is attenuated in p16fl/fl-Cdh5(PAC)-CreERT2 (p16iΔEC) mice after tamoxifen induction. We have reported that endothelial TWIST1 mediates hypoxia-induced vascular remodeling by increasing platelet-derived growth factor (PDGFB) expression. Transcriptomic analyses of IPAH patient or hypoxia-induced mouse lung ECs reveal the alteration of senescence-related gene expression and their interaction with TWIST1. Knockdown of p16INK4A attenuates the expression of PDGFB and TWIST1 in IPAH patient PAECs or hypoxia-treated mouse lungs and suppresses accumulation of αSMA–positive cells to the supplemented ECs in the gel implanted on the mouse lungs. Hypoxia-treated mouse lung EC-derived exosomes stimulate DNA synthesis and migration of PASMCs in vitro and in the gel implanted on the mouse lungs, while p16iΔEC mouse lung EC-derived exosomes inhibit the effects. These results suggest that endothelial senescence controls αSMA–positive cell proliferation and migration in PH through TWIST1-PDGFB signaling.

2022-10-15 | PXD033549 | Pride

Hypoxic pulmonary hypertension study

Project description:These microarray studies were performed using whole lungs of BALB/C mice during development of hypoxia-induced pulmonary hypertension (days 1-21) and resolution of pulmonary hypertension after return to normoxia (days 22-35) . Mice were sampled during nine time-points and each time-point was replicated 4 times (with dye swapping). Keywords = hypoxia Keywords = pulmonary hypertension

2010-06-10 | E-GEOD-1909 | biostudies-arrayexpress

Mechanisms of Myelocytic Nitric Oxide Synthases Against Hypoxia-Induced Pulmonary Hypertension

Project description:The goals of this study are to comprehensively identify genes controlled by myelocytic nitric oxide synthases in the lung against hypoxia-induced pulmonary hypertension, and to identify a novel alternative splicing mechanism.

2017-11-03 | GSE92263 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data