Normal human CFTR overexpression in mouse lung
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE4512 | GEO | 2006/03/24
SECONDARY ACCESSION(S): PRJNA94515
REPOSITORIES: GEO
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Project description:Identification of Genes Responsive to the Expression of Normal Human CFTR Experiment Overall Design: To discern the effects of increased expression of normal human CFTR, lung mRNA levels were assessed in mice expressing the normal human CFTR cDNA under control of the Sftpc gene promoter in respiratory epithelial cells of adult mice. Triplicate samples from SP-C-hCFTRtg/tg, SP-C-hCFTRtg/-, and wild type mice were compared.
2007-11-23 | E-GEOD-4512 | biostudies-arrayexpress
Project description:The objective of this study was to identify changes in gene expression levels between wild-type and CFTR-knockout small intestine. CFTR-knockout mice (provided by Dr. Lane Clarke of the University of Missouri) were maintained on colyte. Keywords: gene expression comparison Four wild-type and four CFTR-knockout small intestinal RNA samples were compared. To facilitate statistical analysis and reduce affects of Cy3 and Cy5 labeling, comparison of two WT and two KO were repeated with a dye flip.
2010-05-25 | E-GEOD-8763 | biostudies-arrayexpress
Project description:The objective of this study was to identify changes in gene expression levels between wild-type and CFTR-knockout small intestine. CFTR-knockout mice (provided by Dr. Lane Clarke of the University of Missouri) were maintained on colyte. Keywords: gene expression comparison
2008-08-08 | GSE8763 | GEO
Project description:The objective of this study was to identify changes in gene expression levels between wild-type and NHE3/CFTR double knockout small intestine. Keywords: gene expression comparison
2008-08-08 | GSE9009 | GEO
Project description:Individuals with cystic fibrosis (CF) experience elevated inflammation in multiple organs, but whether this reflects an inherent feature of CF cells or is a consequence of a pro-inflammatory environment is not clear. Using CRISPR/Cas9-mediated mutagenesis of CFTR, 17 subclonal cell lines were generated from Caco-2 cells. Clonal lines with functional CFTR (CFTR+) were compared to those without (CFTR-) to directly address the role of CFTR in inflammatory gene regulation. All lines maintained CFTR mRNA production and formation of tight junctions. CFTR+ lines displayed short circuit currents in response to forskolin, while the CFTR- lines did not. Baseline expression of both cytokines was not different between the lines regardless of CFTR genotype. All lines responded to TNFa and IL1b by increasing IL6 and CXCL8 (IL8) mRNA levels, but the CFTR- lines produced more CXCL8 mRNA than the CFTR+ lines. Transcriptomes of 6 CFTR- and 6 CFTR+ lines, before and after stimulation by TNFa, were compared for differential expression as a function of CFTR genotype. While some genes appeared to be differentially expressed simply because of CFTR’s absence, others required stimulation for differences to be apparent. Together, these data suggest cells respond to CFTR’s absence by modulating transcriptional networks, some of which are only apparent when cells are exposed to different environmental contexts, such as inflammation. With regards to inflammation, these data suggest a model in which CFTR’s absence leads to a poised, pro-inflammatory state of cells that is only revealed by stimulation.
2019-05-02 | GSE130226 | GEO
Project description:Cystic fibrosis, the most commonly inherited lethal pulmonary disorder in Caucasians, is caused by mutations in the cystic fibrosis transmembrane conductance regulator gene (CFTR). To identify genomic responses to the presence or absence of CFTR in pulmonary tissues in vivo, microarray analyses of lung mRNAs were performed on whole lung tissue from mice lacking (CFTR(-)) or expressing mouse CFTR (CFTR(+)). Whereas the histology of lungs from CFTR(-) and CFTR(+) mice was indistinguishable, statistically significant increases in the relative abundance of 29 and decreases in 25 RNAs were identified by RNA microarray analysis. Of RNAs whose expression was consistently altered by the absence of CFTR, functional classes of genes influencing gene transcription, inflammation, intracellular trafficking, signal transduction, and ion transport were identified. RNAs encoding the transcription factor CCAAT enhancer-binding protein (CEBP) delta and interleukin (IL) 1beta, both known to regulate CFTR expression, were induced, perhaps indicating adaptation to the lack of CFTR. RNAs mediating lung inflammation including calgranulin-S100 family members, IL-1beta and IL-4, were increased. Likewise, expression of several membrane transport proteins that interact directly with CFTR were increased, suggesting that CFTR-protein complexes initiate genomic responses. Absence of CFTR influenced the expression of genes modulating diverse pulmonary cell functions that may ameliorate or contribute to the pathogenesis of CF. Lungs from sex-matched littermates at 3, 6, and 11 weeks of agewere carefully dissected and the conducting airways and mediastinal structures removed.
2007-11-27 | E-GEOD-4513 | biostudies-arrayexpress
Project description:Production of functional proteins requires multiple steps including gene transcription and post-translational processing. MicroRNAs (miRNA) can regulate individual stages of these processes. Despite the importance of the cystic fibrosis transmembrane conductance regulator (CFTR) channel for epithelial anion transport, how its expression is regulated remains uncertain. We discovered that microRNA-138 regulates CFTR expression through its interactions with the transcriptional regulatory protein SIN3A. Treating airway epithelia with a miR-138 mimic increased CFTR mRNA and also enhanced CFTR abundance and transepithelial Cl- permeability independently of elevated mRNA levels. A miR-138 anti-miR had the opposite effects. Importantly, miR-138 altered the expression of many genes encoding proteins that associate with CFTR and may influence its biosynthesis. The most common CFTR mutation, M-NM-^TF508, causes protein misfolding, degradation, and cystic fibrosis. Remarkably, manipulating the miR-138 regulatory network also improved biosynthesis of CFTR-M-NM-^TF508 and restored Cl- transport to cystic fibrosis airway epithelia. This novel miRNA-regulated network directs gene expression from the chromosome to the cell membrane, indicating that an individual miRNA can control a cellular process broader than previously recognized. This discovery also provides new therapeutic avenues for restoring CFTR function to cells affected by the most common cystic fibrosis mutation. 12 samples of Calu-3 cells representing different interventions.
2012-09-04 | E-GEOD-38956 | biostudies-arrayexpress
Project description:The proteins interacting with CFTR and its mutants have been intensively studied using different experimental approaches, enabling to better understand the cellular processes leading to proper protein folding, routing to the plasma membrane, recycling, activation and degradation. Recently, several strategies have been developed based on the proximity labelling of protein partners or proteins in close vicinity and their subsequent identification by mass spectrometry. In this study, we evaluate TurboID and APEX2 proximity labelling approaches on WT CFTR and compare results to those obtained by co-immunoprecipitation and in databases. We then compared the CFTR-WT interactome to two mutants of CFTR (G551D and W1282X) and the structurally unrelated potassium channel KCNK3. The two methods efficiently identified both known and novel CFTR protein partners and in proximity such as multiple SLC transporters. Hence proximity labelling approaches enable to obtain a wider picture of the CFTR interactome, feeding databases and giving a better understanding of the CFTR environment.
2022-10-14 | PXD035184 | Pride
Project description:CFTR IPs with different CFTR mutants or under different conditions to identify CFTR PTMs.
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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