Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

RGS4 controls airway hyperresponsiveness through GAP-independent mechanisms

ABSTRACT: RGS4 controls airway hyperresponsiveness through GAP-independent mechanisms

PROVIDER: PRJNA1013911 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR25939232_1.fastq.gz	Fastqsanger.gz
	SRR25939232_2.fastq.gz	Fastqsanger.gz
	SRR25939233_1.fastq.gz	Fastqsanger.gz
	SRR25939233_2.fastq.gz	Fastqsanger.gz
	SRR25939234_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 24

Similar Datasets

RGS4 controls airway hyperresponsiveness through GAP-independent mechanisms

Project description:Regulators of G protein signaling (RGS proteins) constrain G protein-coupled receptor (GPCR)-mediated and other responses throughout the body primarily, but not exclusively, through their GTPase activating (GAP) activity. Asthma is a highly prevalent condition characterized by airway hyper-responsiveness (AHR) to environmental stimuli resulting in part from amplified GPCR-mediated airway smooth muscle (ASM) contractility. Rgs2 or Rgs5 gene deletion in mice enhances AHR and ASM contraction whereas RGS4 knockout (KO) mice unexpectedly have decreased AHR due to increased production of the bronchodilator prostaglandin E2 (PGE2) by lung epithelial cells. Here we found that knockin mice harboring Rgs4 alleles encoding a point mutation (N128A) that sharply curtails RGS4 GAP activity had increased AHR, reduced airway PGE2 levels, and augmented GPCR-induced bronchial contraction compared to either RGS4 KO mice or WT controls. RGS4 interacted with the p85a subunit of PI3 kinase (PI3K) and inhibited PI3K-dependent PGE2 secretion elicited by TGFb in airway epithelial cells. Together these findings suggest that RGS4 affects asthma severity in part by regulating the airway inflammatory milieu in a G protein-independent manner.

2024-05-08 | GSE242546 | GEO

Mapping of a QTL for airway hyperresponsiveness on mouse chromosome 12

Project description:The BcA86 strain is a unique recombinant congenic strain created from parental strains A/J and C57BL/6J. Naive mice from the BcA86 strain have a lung responsiveness phenotype resembling mice from airway hyperresponsive strain A/J. However, majority of the BcA86 genome is from the hyporesponsive strain C57BL/6J. Our goal was to identify the genomic regions that are associated with this BcA86 phenotype. Using F2 mice generated from BcA86 backcrossed to C57BL/6J, we identified a QTL for airway hyperresponsiveness on mouse chromosome 12. We validated the importance of mouse chromosome 12 in airway responsiveness using a chromosome 12 substitution strain (CSS12) which contains A/J chromosome 12 on a C57BL/6J background. The CSS12 strain also had a lung responsiveness phenotype similar to A/J. We selected genes within our QTL as candidates for airway hyperresponsiveness if they contained a deleterious coding variant (based on PROVEAN analysis) or if they were differently expressed between hyperresponsive (A/J, BcA86, CSS12) and hyporesponsive (C57BL/6J) strains.

2014-11-11 | GSE52356 | GEO

Sex-dependent Influence of LMAN1 on Allergen-induced Airway Hyperresponsiveness

Project description:Sex-dependent Influence of LMAN1 on Allergen-induced Airway Hyperresponsiveness

| PRJNA1250538 | ENA

Distinct Epithelial-Innate Immune Cell Transcriptional Circuits Underlie Airway Hyperresponsiveness in Asthma

Project description:Indirect airway hyperresponsiveness (AHR) is a highly specific feature of asthma but the underlying mechanisms responsible for driving indirect AHR remain incompletely understood. We aimed to identify differences in gene expression in epithelial brushings obtained from individuals with asthma who were characterized for indirect AHR in the form of exercise-induced bronchoconstriction (EIB). RNA-sequencing (RNA-seq) analysis was performed on epithelial brushings obtained from individuals with asthma with (n=11) and without EIB (n = 9).

2023-08-16 | GSE241016 | GEO

Sex-dependent Influence of LMAN1 on Allergen-induced Airway Hyperresponsiveness

Project description:Allergic asthma is a chronic inflammatory disease of the airways characterized by a type 2-high adaptive immune response towards common aeroantigens such as dust mite, pollen and animal dander. Despite the advances made towards translation of various biologics into the clinic, the limited efficacy of these therapies in certain populations, combined with the ineligibility of some patients for treatment (clinically or economically), have led to the continued need for the development of more widely effective allergic asthma therapies. Our lab previously identified lectin mannose-binding 1 (LMAN1) as a novel receptor for house dust mite (HDM) and showed that in vitro, LMAN1 downregulated inflammatory NF-κB signaling in DCs in response to HDM. In this follow-up work, we investigated the in vivo relevance of LMAN1 by subjecting LMAN1 knockout (KO) mice and wild type (WT) littermate controls to a model of HDM-induced allergic asthma. Surprisingly, we discovered that loss of LMAN1 led to opposing effects on airway hyperresponsiveness (AHR) which were dependent on the sex of the mice. HDM-treated female LMAN1 KO mice showed increased AHR, while HDM-treated male KO mice showed decreased AHR, compared with their WT counterparts. We further identified the features of HDM-induced asthma which may account for the gender-biased effects of LMAN1 on lung function. This work not only highlights the complexity of the loss of LMAN1 in vivo but also suggests that such sex-dependent responses should be taken into consideration when pursuing LMAN1 as a therapeutic target for treatment of allergic asthma.

2025-05-12 | GSE294581 | GEO

Effects of allergen and airway constriction on gene expression in mouse lung

Project description:Airway hyperresponsiveness is found to be a heritable trait and the parents of respiratory patients often have this trait. To understand if airway constriction affects the lung and contributes to lung disease, we investigated the lungs that often occur airway constriction and compared those lungs with healthy lung and the lung with inflammation.

2022-11-18 | GSE212406 | GEO

Diacylglycerol kinase ζ promotes allergic airway inflammation and airway hyperresponsiveness through distinct mechanisms.

Project description:Asthma is a chronic allergic inflammatory airway disease caused by aberrant immune responses to inhaled allergens, which leads to airway hyperresponsiveness (AHR) to contractile stimuli and airway obstruction. Blocking T helper 2 (TH2) differentiation represents a viable therapeutic strategy for allergic asthma, and strong TCR-mediated ERK activation blocks TH2 differentiation. Here, we report that targeting diacylglycerol (DAG) kinase zeta (DGKζ), a negative regulator of DAG-mediated cell signaling, protected against allergic asthma by simultaneously reducing airway inflammation and AHR though independent mechanisms. Targeted deletion of DGKζ in T cells decreased type 2 inflammation without reducing AHR. In contrast, loss of DGKζ in airway smooth muscle cells decreased AHR but not airway inflammation. T cell-specific enhancement of ERK signaling was only sufficient to limit type 2 airway inflammation, not AHR. Pharmacological inhibition of DGK diminished both airway inflammation and AHR in mice and also reduced bronchoconstriction of human airway samples in vitro. These data suggest that DGK is a previously unrecognized therapeutic target for asthma and reveal that the inflammatory and AHR components of asthma are not as interdependent as generally believed.

| S-EPMC6996596 | biostudies-literature

Homo sapiens

Project description:Human Airway Hyperresponsiveness

| PRJNA92831 | ENA

Mus musculus

Project description:Murine Airway Hyperresponsiveness

| PRJNA92833 | ENA

Forest gap

Project description:Fungi community variation of Forest gap soil

| PRJEB25917 | ENA