Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA347839 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:We have used microarrays to identify individual genes and pathways regulated by Gq/11 or G12/13 signalling in type II alveolar epithelial cells isolated from the lungs of knockout mice.
2016-10-25 | GSE87842 | GEO
Project description:Background: Gq-coupled G protein-coupled receptors (GPCR) mediate the actions of a variety of messengers that are key regulators of cardiovascular function. Enhanced Gaq-mediated signaling plays an important role in cardiac hypertrophy and in the transition to heart failure. We have recently described that Gaq acts as an adaptor protein that facilitates PKCz-mediated activation of ERK5 in epithelial cells. Since the ERK5 cascade is known to be involved in cardiac hypertrophy, we have investigated the potential relevance of this pathway in Gq-dependent signaling in cardiac cells. Methodology/Principal Findings: We have explored the mechanisms involved in Gq-coupled GPCR-mediated stimulation of the ERK5 pathway and its functional consequences in cardiac hypertrophy using both cultured cardiac cells and an animal model of angiotensin- dependent induction of cardiac hypertrophy in wild-type and PKCz knockout mice. We find that PKC? is required for the activation of the ERK5 pathway by Gq-coupled GPCR in cardiomyocytes and in cardiac fibroblasts. Stimulation of ERK5 by angiotensin II is blocked upon pharmacological inhibition or siRNA-mediated silencing of PKCz in primary cultures of cardiac cells and in cardiomyocytes isolated from PKCz-deficient mice. Moreover, these mice do not develop cardiac hypertrophy upon chronic challenge with angiotensin II, as assessed by morphological, biomarker, electrocardiographic and global gene expression pattern analysis. Conclusion/Significance: Our data put forward that PKC? is essential for Gq- dependent ERK5 activation in cardiac cells and indicate a key cardiac physiological role for this recently described Gaq/PKCz/MEK5 signaling axis. Littermate wild-type and PKCz -/- male mice (32 weeks of age) were subjected to continuous infusion of angiotensin II (or PBS as a control) for 14 days, a well established model for the induction of cardiac hypertrohy
2012-01-10 | E-GEOD-29145 | biostudies-arrayexpress
Project description:We investigated whether in vitro expansion of human alveolar epithelial type II cells is possible. We found that human endogenous human alveolar epithelial type II cells can be cultured and passaged. The culture system enabled retroviral gene transduction into human alveolar epithelial type II cells. We performed RNA sequencing of human alveolar epithelial type II cells transduced with mutant surfactant protein C or control vector.
2019-06-27 | GSE128291 | GEO
Project description:Comparison of rat freshly-isolated alveolar epithelial type I cells, freshly-isolated type II cells, and type II cells cultured for 7 days Keywords = rat, alveolar epithelial type I cells, cultured type II cells Keywords: parallel sample
2004-11-01 | GSE1567 | GEO
Project description:Development of the vertebrate jaw apparatus depends on highly conserved signaling pathways. Patterning of the lower jaw is driven by Endothelin receptor type A (Ednra) and secreted ligand Endothelin 1 (Edn1). The Ednra signaling pathway establishes the identity of lower jaw progenitors by regulating expression of numerous patterning genes, but the intracellular signaling mechanisms linking receptor activation to gene regulation remains poorly understood. As a first step towards addressing this question, we examined the function of the Gq/11 family of Gα subunits in zebrafish using pharmacological and genetic ablation of Gq/11 activity and transgenic induction of a constitutively active Gq protein in edn1-/- embryos. Loss of Gq/11 activity fully recapitulated the edn1-/- phenotype, with genes encoding for G11 being most essential. Furthermore, inducing Gq activity in edn1-/- embryos not only restored Ednra-dependent jaw structures and gene expression signatures but also caused homeosis of the upper jaw structures into a lower jaw-like structure. These results indicate that Gq/11 is necessary and sufficient to mediate the lower jaw patterning mechanism for Ednra.
2024-09-19 | GSE275013 | GEO
Project description:Pathologic transformation represents a critical yet poorly defined window during which mutant epithelial stem cells actively construct the microenvironment that enables tumour initiation. Here, using integrated single-cell, spatial, and functional analyses, we define the earliest multicellular events that license this transition following oncogenic activation in the lung. KrasG12D-mutant alveolar type II cells rapidly adopt regenerative-like states that act as signalling hubs, orchestrating coordinated stromal and immune reprogramming while enhancing epithelial plasticity. Through secretion of Amphiregulin (Areg), mutant epithelial cells activate EGFR signalling in adjacent fibroblasts, inducing a fibrotic, injury-like programme. Reprogrammed fibroblasts, in turn, expand and reprogramme alveolar macrophages, amplifying inflammatory signalling and reinforcing epithelial plasticity. These reciprocal interactions establish a self-sustaining epithelial–stromal–immune circuit that generates a tumour-permissive niche prior to malignant outgrowth. Disruption of the Areg–EGFR axis prevents early niche formation and abrogates tumour initiation. Conservation of this programme in KRASG12D-inducible human alveolar organoids and early-stage lung adenocarcinoma tissues identifies epithelial–microenvironment communication as a therapeutically actionable vulnerability and suggests that intercepting niche formation may prevent progression to treatment-resistant disease.
2026-02-25 | GSE310335 | GEO
Project description:Activation of heterotrimeric G-proteins (Gαβγ) by G-protein-coupled receptors (GPCRs) is a quintessential mechanism of transmembrane signal transduction in eukaryotes with major biomedical implications in therapeutic targeting. We developed a suite of publicly-accessible transgenic mouse lines that, collectively, allow for the conditional expression of biosensors, named BRET sensors with ER/K linker and YFP 3 (BERKY3), for any class of GPCR-activated G-protein (Gs, Gi/o, Gq/11, or G12/13). These permit detection of endogenous G-protein activation by endogenous GPCRs in diverse contexts, like in different brain cell types or in lung cells under native-like tissue conditions. To address whether the expression of BERKY biosensors in cells isolated from the transgenic mice affected the signaling mechanism under investigation, unbiased transcriptomic analyses were performed, revealing the high fidelity of the biosensor readout. In summary, the experimental platform of genetically-modified mice introduced here provides a versatile resource to reproducibly interrogate biological processes or mechanisms of drug action that operate via GPCR/G-protein signaling under native cellular conditions and across physiologically-relevant systems.
2026-01-08 | GSE286196 | GEO
Project description:Expression data from alveolar type II epithelial cells
| PRJNA95401 | ENA
Project description:The influenza-infected mouse model serves as an acute lung injury model, leading to extensive collapse of the alveolar regions. In this project, we aimed to investigate the effects of influenza infection on the transcriptome of type II alveolar epithelial cells. We isolated type II alveolar epithelial cells at various time points post-infection for transcriptome sequencing.
2026-02-26 | GSE295598 | GEO
Project description:G protein-coupled receptors (GPCRs) are the largest receptor superfamily that can propagate various extracellular stimulus into cells by coupling with heterotrimeric G proteins. G proteins are divided into four families, Gs, Gi/o, Gq/11 and G12/13, which are responsible for the transduction of discrete downstream signaling pathways. Interestingly, one receptor can couple to more than one G protein subtype with different coupling efficiency or kinetics; coupling with the highest efficiency and/or kinetics is known as ‘primary coupling’ whereas the one with lower efficiency and/or slower kinetics is known as ‘secondary coupling’. Due to its significance in human physiology, there has been a great effort to elucidate the precise mechanism of GPCR-G protein coupling, however, the complex nature of GPCR and G protein interaction raises more unanswered questions. Here, we utilized hydrogen/deuterium exchange mass spectrometry (HDX-MS) to understand the molecular mechanism underlying primary and secondary Gi/o coupling using muscarinic acetylcholine receptor type 2 (M2R) and β2-adrenergic receptor (β2AR) as the primary and secondary Gi/o-coupling receptors, respectively. Results showed the engagement of the distal C-terminus of Gi/o with the receptor differentiates primary and secondary Gi/o couplings. In addition, the interaction between the intracellular loop 2 (ICL2) of the receptor and Gi/o in primary Gi/o coupling is not as critical as in primary Gs coupling.
2020-07-02 | PXD019367 | Pride