Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Gpr116 regulates pulmonary surfactant pool size

ABSTRACT: The amount of pulmonary surfactant within type II cells and in the alveolar space, referred to as surfactant pool sizes, are tightly regulated. The molecular pathways that sense and regulate surfactant pool size within the alveolus have not been identified and constitute a fundamental knowledge gap in the field. Our data show that mice with a germline mutation in the orphan G-protein-coupled receptor, GPR116, have a 30-fold accumulation of surfactant phospholipids that causes respiratory distress in adult animals. This phenotype is associated with increased surfactant secretion and induction of the purinergic receptor P2RY2 in young animals, and lipid-laden macrophages and alveolar destruction in older animals. We further demonstrate that GPR116 mRNA expression is developmentally regulated in the murine lung with peak expression at birth when surfactant pool sizes are maximal. Within the lung, GPR116 protein expression is restricted to the apical plasma membrane of alveolar type I and type II epithelial cells.

ORGANISM(S): Mus musculus

PROVIDER: GSE41417 | GEO | 2013/04/10

SECONDARY ACCESSION(S): PRJNA177187

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Gpr116 regulates pulmonary surfactant pool size

Project description:The amount of pulmonary surfactant within type II cells and in the alveolar space, referred to as surfactant pool sizes, are tightly regulated. The molecular pathways that sense and regulate surfactant pool size within the alveolus have not been identified and constitute a fundamental knowledge gap in the field. Our data show that mice with a germline mutation in the orphan G-protein-coupled receptor, GPR116, have a 30-fold accumulation of surfactant phospholipids that causes respiratory distress in adult animals. This phenotype is associated with increased surfactant secretion and induction of the purinergic receptor P2RY2 in young animals, and lipid-laden macrophages and alveolar destruction in older animals. We further demonstrate that GPR116 mRNA expression is developmentally regulated in the murine lung with peak expression at birth when surfactant pool sizes are maximal. Within the lung, GPR116 protein expression is restricted to the apical plasma membrane of alveolar type I and type II epithelial cells. To better understand the roles and molecular mechanisms by which Gpr116 influences gene expression in lung, the effect of cell-selective deletion of Gpr116 (Gpr116D/D) on genome-wide mRNA expression profiles was determined in murine type II alveolar epithelial cells. Differentially expressed genes were identified from Affymetrix Murine GeneChips analysis and subjected to gene ontology classification promoter analysis, pathway mapping and literature mining.

2013-04-10 | E-GEOD-41417 | biostudies-arrayexpress

Regeneration of the lung alveolus by an evolutionarily conserved epithelial progenitor [ATAC-seq]

Project description:The lung alveolus is the primary site of gas exchange in mammals. Within the alveolus, the alveolar type 2 (AT2) epithelial cell population generates surfactant to maintain alveolar structure and harbors a regenerative capacity to repair the alveolus after injury. We show that a Wnt-responsive alveolar epithelial progenitor (AEP) lineage within the AT2 cell population is critical for regenerating the alveolar niche. AEPs are a stable lineage during alveolar homeostasis but expand rapidly to regenerate a majority of the alveolar epithelium after acute lung injury. AEPs exhibit a distinct transcriptome, epigenome, and functional phenotype with specific responsiveness to Wnt and FGF signaling that modulates differentiation and self-renewal, respectively. Importantly, human AEPs (hAEPs) can be isolated and characterized through a conserved surface marker and are required for human alveolar self-renewal and differentiation using alveolar organoid assays. Together, our findings show that AEPs are an evolutionarily conserved alveolar progenitor lineage essential for regenerating the alveolar niche in the mammalian lung.

2018-01-08 | GSE97052 | GEO

Regeneration of the lung alveolus by an evolutionarily conserved epithelial progenitor [mouse RNA-seq]

2018-01-08 | GSE97054 | GEO

Regeneration of the lung alveolus by an evolutionarily conserved epithelial progenitor [human RNA-seq]

2018-01-08 | GSE97053 | GEO

Endothelial Sash1 is required for alveolar surfactant production through nitric oxide signaling

Project description:Sash1 acts as a scaffold in TLR4 signaling. We generated Sash1-/- mice, which die in the perinatal period due to respiratory distress. Constitutive or endothelial-restricted Sash1 loss leads to a reduction of surfactant-associated protein synthesis. We show that Sash1 interacts with β-arrestin 1 downstream of the TLR4 pathway to activate Akt and eNOS in microvascular endothelial cells. Generation of nitric oxide downstream of Sash1 in endothelial cells activated cGMP in adjacent alveolar type 2 cells to induce transcription of surfactant genes. Thus we identify a critical cell nonautonomous function for Sash1 in embryonic development in which endothelial Sash1 affects alveolar type 2 cells and promotes pulmonary surfactant production through nitric oxide signaling. Lack of pulmonary surfactant is a major cause of respiratory distress and mortality in preterm infants, and these findings identify the endothelium as a potential target for therapy.

2019-05-01 | GSE123889 | GEO

Lung collapse and respiratory distress in neonatal cloned cows is caused by surfactant homeostasis disorders

Project description:Respiratory distress is one of the major causes of the high mortality rate in neonatal cloned animals. Although some therapeutic methods have been used to improve the survival of cloned neonatal animals, the mechanisms of their neonatal respiratory distress lacked thorough investigation. Pathological analyses including necropsy and histology were implemented to determine the precise disease phenotypes, by which not fully dilated lungs, alveolar collapse and thickened alveolar walls were detected in neonatal cloned cows dying of respiratory distress compared to naturally conceived neonatal cows. In addition, we compared mRNA expression profiles between the two groups and differentially expressed genes (DEGs) have been achieved. Based on DEGs, GO and KEGG pathway enrichment analyses were performed, which showed that processes and pathways associated with surfactant homeostasis were significantly enriched between the two groups (p < 0.05).

2019-10-14 | GSE88912 | GEO

Pseudomonas aeruginosa response to lung surfactant

Project description:The response of bacteria to the conditions at the site of infection is a key part of the transcriptional program that will determine the sucess of the infectious agent. To model the environment of the distal airway, we used bovine pulmonary surfactant (Survanta). P. aeruginosa transcript levels were measured in the presence or absence of Survanta in MOPS minimal medium to identify transcripts altered in response to surfactant. The most highly induced transcript in Survanta was PA5325, renamed sphA based on our findings that the gene was specifically induced by sphingosine derived from the sphingomyelin present in pulmonary surfactant. A divergently transcribed transcription factor, PA5324, was demonstrated to be critical for the sphingosine dependent induction of sphA and was therefore renamed SphR. Microarrays of the sphR mutant cells were compared to wild type to determine the likely SphR regulon. Wild type and sphR mutant cells were pre-grown in MOPS minimal media and then split and resuspended in MOPS pyruvate or MOPS pyruvate + surfactant

2013-12-10 | E-GEOD-48982 | biostudies-arrayexpress

Surfactant Protein C knockout

Project description:Study the Role of Surfactant Protein C in Innate Lung Defense. Gene expression profiles comparison between isolated TYPE II cells from SPC(-/-) and control litter mates.

2012-08-21 | E-GEOD-35989 | biostudies-arrayexpress

Surfactant plus budesonide decreases lung and systemic responses to injurious ventilation in preterm sheep

Project description:Background: Intratracheal budesonide mixed with surfactant has been investigated as an alternative to decrease lung injury and prevent bronchopulmonary dysplasia in preterm infants. However, possible systemic effects are not known. Our goal was identify systemic effects of intra-tracheal instilled budesonide by transcriptome analysis of the brain and lung in a preterm lamb model of mechanical ventilation. Methods: We performed RNA-sequencing of the fetal periventricular white matter and liver from preterm sheep after treatment with intratracheal budesonide mixed with surfactant or surfactant alone followed by mechanical ventilation. Unventilated animals were used as controls. mRNA profiles were generated from polyA selected RNA using Illumina platform. Read sequences were aligned to the sheep genome (Oar 4.0) using Bowtie2 followed read counts using featureCounts. We performed differential expression analysis using EdgeR. Results: We identified large and significant gene expression genes both in the liver and in the priventricular white matter in animals treated with budesonide+surfactant compared to surfactant alone and unventilated animals. There were complexes synergies and antagonism of effect of ventilation and budesonide on gene expression. Ventilation induced inflammatory signaling in the periventricular white matter and liver which was partially antagonized by budesonide. Budesonide also suppressed developmental pathways in the periventricular white matter. Conclusions: Intratracheal budesonide had systemic effects including suppression of developmental pathways in the brain. These effects could have clinical implication in affecting the neurodevelopmental outcomes of preterm newborns.

2019-11-26 | GSE131195 | GEO

Pseudomonas aeruginosa response to lung surfactant

2013-12-10 | GSE48982 | 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