NRG1-induced gene expression changes in human airway epithelial cells
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA549681 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR9327703.fastq.gz | Fastqsanger.gz | |||
| SRR9327704.fastq.gz | Fastqsanger.gz | |||
| SRR9327705.fastq.gz | Fastqsanger.gz | |||
| SRR9327706.fastq.gz | Fastqsanger.gz | |||
| SRR9327707.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 6 |
Similar Datasets
Project description:RNA sequencing was performed using RNA obtained from AALE cells carrying an empty control construct or a construct promoting the overexpression of NRG1.
2021-06-08 | GSE133002 | GEO
Project description:Aberrant epithelial polarity promotes precancerous airway lesions via YAP/TAZ-induced NRG1-ERBB signaling
| PRJNA551614 | ENA
Project description:Characterization of DNA methylation changes induced by albuterol in airway epithelial cultures
| PRJNA1002382 | ENA
Project description:Albuterol is the first-line asthma medication used in diverse populations. Although DNA methylation (DNAm) is an epigenetic mechanism involved in asthma and bronchodilator drug response (BDR), no study has assessed whether albuterol could induce changes in the airway epithelial methylome. We aimed to characterize albuterol-induced changes in DNAm in airway epithelial cells and assess the potential functional consequences and biological pathways implicated. We followed a discovery and validation study design to characterize albuterol-induced DNAm changes in paired airway epithelial cultures stimulated in vitro with albuterol. In the discovery phase, an epigenome-wide association study (EWAS) using paired nasal epithelial cultures from Puerto Rican children (n=97) identified 22 CpGs genome-wide associated with repeated-use albuterol treatment (p<9x10-8). Albuterol predominantly induced a hypomethylation effect on CpGs captured by the EPIC array across the genome (probability of hypomethylation: 76%, p-value=3.3x10-5). DNAm changes on the CpGs cg23032799 (CREB3L1), cg00483640 (MYLK4-LINC01600), and cg05673431 (KSR1) were validated in nasal epithelia from 10 independent donors (false discovery rate [FDR]<0.05). The effect on the CpG cg23032799 (CREB3L1) was cross-tissue validated in bronchial epithelial cells at nominal level (p=0.030). DNAm changes in these three CpGs showed to be influenced by three independent genetic variants (FDR<0.05). In silico analyses showed these polymorphisms regulated gene expression of nearby genes in lungs and/or fibroblasts including KSR1 and LINC01600 (6.30x10 14≤p≤6.60x10-5). Additionally, the hypomethylation at the CpGs cg10290200 (FLNC) and cg05673431 (KSR1) was associated with reduced gene expression of the genes where they are located (FDR<0.05). Furthermore, while the epigenetic effect of albuterol was independent of the asthma status, severity, and use of medication, BDR was nominally associated with the effect on the CpG cg23032799 (CREB3L1) (p=0.004). Gene-set enrichment analyses revealed that epigenomic modifications of albuterol could participate in asthma-relevant processes (e.g., IL-2, TNF-α, and NF-κB signaling pathways) and that albuterol-affected genes are likely regulated by Trichostatin A (FDR<0.05). Finally, nine differentially methylated regions were associated with albuterol treatment, including CREB3L1, MYLK4, and KSR1 (adjusted p-value<0.05). In conclusion, this study reveals, for the first time, evidence of epigenetic modifications induced by albuterol in the mucociliary airway epithelium. The epigenomic response induced by albuterol might have potential clinical implications by affecting biological pathways relevant to asthma
2023-10-18 | GSE240155 | GEO
Project description:In inflammatory diseases of the airway, a high level (estimated to be as high as 8 mM) of HOCl can be generated through a reaction catalyzed by the leukocyte granule enzyme myeloperoxidase (MPO). HOCl, a potent oxidative agent, causes extensive tissue injury through its reaction with various cellular substances, including thiols, nucleotides, and amines. In addition to its physiological source, HOCl can also be generated by chlorine gas inhalation from an accident or a potential terrorist attack. Despite the important role of HOCl-induced airway epithelial injury, the underlying molecular mechanism is largely unknown. In the present study, we found that HOCl induced dose-dependent toxicity in airway epithelial cells. By transcription profiling using GeneChip, we identified a battery of HOCl-inducible antioxidant genes, all of which have been reported previously to be regulated by nuclear factor erythroid-related factor 2 (Nrf2), a transcription factor that is critical to the lung antioxidant response. Consistent with this finding, Nrf2 was found to be activated time and dose dependently by HOCl. Although the epidermal growth factor receptor-MAPK pathway was also highly activated by HOCl, it was not involved in Nrf2 activation and Nrf2-dependent gene expression. Instead, HOCl-induced cellular oxidative stress appeared to lead directly to Nrf2 activation. To further understand the functional significance of Nrf2 activation, small interference RNA was used to knock down Nrf2 level by targeting Nrf2 or enhance nuclear accumulation of Nrf2 by targeting its endogenous inhibitor Keap1. By both methods, we conclude that Nrf2 directly protects airway epithelial cells from HOCl-induced toxicity.
2008-06-03 | GSE11630 | GEO
Project description:Hyperglycemia is a risk factor for breast cancer-related morbidity and mortality. Hyperglycemia induces Neuregulin 1 (Nrg1) overexpression in breast cancer, which subsequently promotes tumor progression. However, molecular mechanisms underlying hyperglycemia-induced Nrg1 overexpression remain poorly understood. Here, We used DNA-protein pull-down using Nrg1 enhancer sequence as bait followed by LC/MS and identified RBPJ as a key component of the Nrg1 enhanceosome. We show that hyperglycemia causes active histone modifications at the Nrg1 enhancer, forming enhanceosome complexes where RBPJ, P300, and SETD1A are recruited to upregulate Nrg1 expression.
2023-01-29 | PXD038668 | Pride
Project description:Acinar cells are the principal secretory unit of multiple exocrine organs. A single cell layered, lumenized acinus forms from a large cohort of epithelial progenitors that must initiate and coordinate three cellular programs of acinar specification, namely, lineage progression, secretion, and polarization. Despite this well-known outcome, the mechanism(s) regulating these complex programs are unknown. Here, we demonstrate that neuronal-epithelial cross-talk drives acinar specification through neuregulin (NRG1)-ERBB3-mTORC2 signaling. Using single-cell and global RNA-sequencing of developing salivary glands, we identified NRG1-ERBB3 to precisely overlap with acinar specification during gland development. Genetic deletion of Erbb3 prevented cell lineage progression and the establishment of lumenized, secretory acini. Conversely, NRG1 treatment of isolated epithelia was sufficient to recapitulate the development of secretory acini. Mechanistically, we found NRG1-ERBB3 regulates each developmental program through an mTORC2 signaling pathway. Thus, we reveal a novel neuronal-epithelial (NRG1/ERBB3/mTORC2) mechanism to orchestrate the creation of functional acini.
2022-10-11 | GSE214976 | GEO
Project description:Epithelial miR-141 regulates IL-13-induced airway mucus production
| PRJNA682625 | ENA
Project description:Despite the appreciated in vivo role of the redox-active Pseudomonas virulence factor pyocyanin in Pseudomonas airway infections and the recognized importance of airway epithelial cells in combating bacterial pathogens, little is known about pyocyaninM-bM-^@M-^Ys effect on airway epithelial cells. We find that exposure of bronchiolar epithelial cells to pyocyanin results in MUC2/MUC5AC induction and mucin secretion mediated by reactive oxygen species production, activation of the epidermal growth factor receptor pathway and release of inflammatory cytokines (IL-1b, IL-6, TGFa, TNFa). Microarray analysis identified 286 pyocyanin-induced genes in airway epithelial cells, including many of the inflammatory mediators elevated in cystic fibrosis airways (G-CSF, GM-CSF, CXCL1, SAA). We also found several novel pyocyanin-responsive genes of potential importance in the infection process (IL-24, CXCL2, CXCL3, CCL20, SOD2). This comprehensive study uncovers numerous details of pyocyaninM-bM-^@M-^Ys proinflammatory action and establishes airway epithelial cells as key responders following exposure to this microbial toxin. H292 cells were treated with or without 8 uM pyocyanin for 48 hrs in serum-free RPMI medium. RNA was isolated in four independent experiments, collected, processed and subjected to microarray analysis simultaneously (biological repeats).
2011-06-01 | E-GEOD-22430 | biostudies-arrayexpress
Project description:A study employs quantitative phosphoproteomics approch for systems biology understanding of epithelial mesenchymal transition of human primary small airway epithelial cells
2018-10-25 | PXD003296 | Pride