Gene expression data from human bronchial epithelial cell lines: comparison between normal and CFTR-deficient cells
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE110289 | GEO | 2019/01/31
REPOSITORIES: GEO
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Project description:The purpose of this study was to explore baseline expression of miRNome in Cystic Fibrosis Bronchial Epithelial (CFBE41o-) cells stably transfected with wild type (WT) Cystic Fibrosis Transmembrane Conductance regulator (CFTR) and F508del-CFTR. To fulfill this goal miRNA sequencing was done to see miRNA landscape in CFBE41o- Cells with homozygous F508del mutated CFTR and in CFBE41o- Cells with homozygous WT-CFTR, without any treatment condition.
2019-03-28 | GSE128912 | GEO
Project description:Cystic Fibrosis (CF) is a genetic disorder CF is caused by mutations of the gene encoding for the cystic fibrosis transmembrane conductance regulator protein (CFTR), a transmembrane anion channel expressed at the apical membrane of several organs, including the epithelial cells of the airway. CFTR mutations result in dysfunctional ion transport across the apical membrane at the surface of the epithelia, generating thickened and dehydrated secretions. In the lung, this leads to a decrease in the mucociliary clearance, favoring bacterial colonization and progressive obstruction of the duct. Although over 2000 CFTR variants have been identified so far, the most common mutation is a deletion of the phenylalanine in position 508 (F508del), which shows an allelic frequency of around 90% among CF patients. F508del-CFTR is incorrectly folded, causing its retention at the endoplasmic reticulum (ER) and subsequent proteasomal degradation. Among the several drugs available in CF pharmacological treatment, VX-809 (commercial name Lumacaftor) is the most used drug for patients carrying F508del-CFTR mutation. This drug corrects the aberrant folding of F508del-CFTR by favoring the correct intramolecular interactions, thus enabling a higher number of copies of the defective protein to reach the plasma membrane. We applied SWATH-based proteomics to understand if a pharmacological rescue of F508del-CFTR is associated with changes in global protein expression of the human bronchial epithelium by using the CFBE41o- cell model, a line that stably expresses F508del-CFTR.
2022-08-11 | PXD028355 | Pride
Project description:Cystic fibrosis bronchial epithelial (CFBE41o-ΔF508) cells subjected to 23 bio-active small molecules including vehicle controls, at low temperature and untreated cells. Untreated Cystic fibrosis bronchial epithelial cells (CFBE41o−CFTR) are also included.
2016-12-12 | GSE67698 | GEO
Project description:Cystic Fibrosis (CF) is a genetic disorder CF is caused by mutations of the gene encoding for the cystic fibrosis transmembrane conductance regulator protein (CFTR), a transmembrane anion channel expressed at the apical membrane of several organs, including the epithelial cells of the airway. CFTR mutations result in dysfunctional ion transport across the apical membrane at the surface of the epithelia, generating thickened and dehydrated secretions. In the lung, this leads to a decrease in the mucociliary clearance, favoring bacterial colonization and progressive obstruction of the duct. Although over 2000 CFTR variants have been identified so far, the most common mutation is a deletion of the phenylalanine in position 508 (F508del), which shows an allelic frequency of around 90% among CF patients. F508del-CFTR is incorrectly folded, causing its retention at the endoplasmic reticulum (ER) and subsequent proteasomal degradation. Among the several drugs available in CF pharmacological treatment, VX-809 (commercial name Lumacaftor) is the most used drug for patients carrying F508del-CFTR mutation. This drug corrects the aberrant folding of F508del-CFTR by favoring the correct intramolecular interactions, thus enabling a higher number of copies of the defective protein to reach the plasma membrane. Localization of Organelle Proteins by Isotope Tagging after Differential ultra-Centrifugation (LOPIT-DC, https://doi.org/10.1038/s41467-018-08191-w) workflow was used to study the spatial localization of proteins in the CFBE41o- cells and how it is impacted by CFTR rescue triggered by VX-809. LOPIT-DC is a powerful and well-established tool for the investigation of the spatial distribution of global proteome within cells, which combines subcellular fractionation based on differential centrifugation, quantitative mass spectrometry, and machine learning. Its application provides a global snapshot of the steady-state subcelluler distribution of proteins. The aim of this project is to identify proteins that change their cellular localization in association with the treatment, to uncover molecules that play a role in the trafficking of the defective CFTR to the plasma membrane.
2022-08-11 | PXD028393 | Pride
Project description:Whole transcriptional analysis of cystic fibrosis (CF) patients-derived CFBE41o- cells under the linc-SUMF1-2 knockdown condition. We utilized the gene expression data to understand the linc-SUMF1-2 function in CF bronchial epithelial cells.
2019-01-31 | GSE110288 | GEO
Project description:In the clinical setting, mutations in the CFTR gene enhance the inflammatory response to P. aeruginosa (PA01) infection, but measurements of the inflammatory response to pathogen stimulation by isolated airway epithelia can yield variable results. In this series, we exposed CFBE41o- cells over-expressing ∆F508/∆F508 CFTR and CFBE41o- cells rescued with wt-CFTR to P. aeruginosa biofilms. P. aeruginosa elicited a more robust increase in cytokine and chemokine expression (e.g., IL-8, CXCL2, CXCL3, CXCR4 and TNF-α) in CFBE-wt-CFTR cells compared to CFBE-∆F508-CFTR cells. These results demonstrate that CFBE41o- cells complemented with wt-CFTR mount a more robust inflammatory response to P. aeruginosa than CFBE41o- ∆F508/∆F508-CFTR cells.
2011-08-01 | GSE30439 | GEO
Project description:Cystic fibrosis (CF)-related diabetes (CFRD) is an increasingly common and devastating comorbidity of CF, affecting ~35% of adults with CF. However, the underlying causes of CFRD are unclear. Here, we examined cystic fibrosis transmembrane conductance regulator (CFTR) islet expression and whether the CFTR participates in islet endocrine cell function using murine models of b cell CFTR deletion, and normal and CF human pancreas and islets. Specific deletion of CFTR from murine b cells did not affect b cell function. In human islets, CFTR mRNA was minimally expressed, and CFTR protein/electrical activity was not detected. Isolated CF/CFRD islets demonstrated appropriate insulin and glucagon secretion with few changes in key islet-regulatory transcripts. Furthermore, ~65% of b cell area was lost in CF donors, compounded by pancreatic remodeling and immune infiltration of the islet. These results indicate that CFRD is not caused by intrinsic islet dysfunction from CFTR mutation, but rather, by b cell loss and intra-islet inflammation in the setting of a complex pleiotropic disease
2018-04-25 | GSE110935 | GEO
Project description:In the clinical setting, mutations in the CFTR gene enhance the inflammatory response to P. aeruginosa (PA01) infection, but measurements of the inflammatory response to pathogen stimulation by isolated airway epithelia can yield variable results. In this series, we exposed CFBE41o- cells over-expressing ?F508/?F508 CFTR and CFBE41o- cells rescued with wt-CFTR to P. aeruginosa biofilms. P. aeruginosa elicited a more robust increase in cytokine and chemokine expression (e.g., IL-8, CXCL2, CXCL3, CXCR4 and TNF-?) in CFBE-wt-CFTR cells compared to CFBE-?F508-CFTR cells. These results demonstrate that CFBE41o- cells complemented with wt-CFTR mount a more robust inflammatory response to P. aeruginosa than CFBE41o- ?F508/?F508-CFTR cells. CFBE41o- cells generously provided by Dr. J.P. Clancy (University of Alabama). The series involved 4 treatment groups: unexposed wild type CFTR cells, unexposed ?F508/?F508 CFTR cells, wild type CFTR cells exposed to PA01, and ?F508/?F508 CFTR cells exposed to PA01. Each treatment group involved 4 replicate polarized monolayers. PAO1 was added to the apical side of exposed monolayers at a multiplicity of infection (MOI) of 30:1 for 1 hour in the absence of antibiotics, and then planktonic PAO1 was removed by replacing the apical medium with MEM supplemented with 0.4% arginine (2). Control monolayers were treated identically except that vehicle only (medium used to grow PAO1, MEM supplemented with 0.4% arginine) was added to the apical side of cells. Five hours after washing planktonic P. aeruginosa from the cell monolayers mRNA was isolated.
2011-07-31 | E-GEOD-30439 | biostudies-arrayexpress
Project description:Cystic fibrosis (CF) is a life-shortening genetic disease caused by a mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Despite reports of CFTR expression on endothelial cells, pulmonary vascular perturbations, and perfusion deficit in CF patients, the mechanism of pulmonary vascular disease in CF remains unclear. Here, we describe loss of small pulmonary blood vessels in CF patients with severe lung disease. Using a vessel-on-a-chip model, we establish a shear stress-dependent mechanism of endothelial barrier failure in CF involving calcium-permeable mechanosensitive channel TRPV4. Furthermore, we demonstrate that CFTR deficiency downregulates the function of PIEZO1, another calcium-permeable mechanosensitive channel involved in angiogenesis and wound repair, and further exacerbates loss of small pulmonary blood vessels. We show that CFTR directly interacts with PIEZO1 and enhances its function, and that CFTR deficiency reduces PIEZO1 activity. Our study identifies key cellular targets to mitigate loss of small pulmonary blood vessels in CF.
2024-09-18 | GSE244214 | GEO
Project description:Cystic fibrosis (CF) is characterized by chronic inflammation and excessive cytokines secretion in the lung. Isogenic human CF bronchial epithelial (CFBE41o-) cell lines stably expressing wt-CFTR (WTBE) or F508del mutant (CFBE) are widely used tools in understanding responses to stimuli or drugs and CF pathogenesis in vitro. However, their intrinsic cellular differences in culture are unknown. Hence, we performed integrative analyses at protein, mRNA and chromatin levels on these isogenic cell lines cultured in submerged and transwell condition. CFBE and WTBE cells displayed different secretion patterns on IL-6, IL-8, CXCL1, CXCL10, and CCL5 . The ALI culture dramatically increased cytokines secretion in both cells. ATAC-seq results showed that CFBE cells exhibited higher genome-wide chromatin accessibility than WTBE cells in both culture methods, but the relative openness of cytokine genes between two cells varied individually. Differentially expressed genes between two cell lines from mRNA sequencing were highly concentrated in immunity-related pathways. While the mRNA stability of CXCL10 and CXCL1 exhibited the most significant differences between cell lines in SUB culture, most cytokines had comparable mRNA stabilities within same culture method. Moreover, polarization of cells via transwell culture remodeled the chromatin accessibility and transcriptome. This multilayered studies presents a comprehensive baseline activities of CFBE and WTBE cells, further facilitating their usage and data interpretation as CF cell models.
2022-03-01 | GSE186918 | GEO