KAFPATH-CF
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB95094 | ENA |
REPOSITORIES: ENA
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Project description:Cystic Fibrosis Related Diabetes (CFRD), the main co-morbidity in Cystic Fibrosis (CF), is associated with higher rates of lung function decline. We hypothesize that airway epithelial barrier function is impaired in CF and is further exacerbated under hyperglycemia, worsening pulmonary outcomes. Using 16HBE cells as a model cell line, we studied the effects of hyperglycemia in airway epithelial barrier function. Results show increased paracellular dye flux in CF cells in response to insulin treatment under hyperglycemia, suggesting impaired barrier integrity. Gene expression experiments identified Claudin-4 (CLDN4) as a key tight junction protein dysregulated in CF cells. Further investigation into CLDN4 protein localization by confocal microscopy showed that CLDN4 was tightly localized at tight junctions in WT cells and localization did not change under hyperglycemia. ln contrast, CLDN4 was less well-localized in CF cells at normal glucose and localization was worsened in CF cells conditioned to hyperglycemia. Treatment with highly effective modulator compounds (ETI) reversed this trend, and CFTR rescue by ETI in CF cells was not affected by insulin treatment or hyperglycemia. Bulk RNA sequencing showed differences in transcriptional responses in CF compared to WT cells under normal or high glucose, highlighting PTPRG as a promising target for further investigation.
2024-06-03 | GSE268909 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE28306: Expression data from Burkholderia multivorans cystic fibrosis clinical isolates GSE30402: Hybridization of Burkholderia multivorans D2095 and D2214 genomic DNA Refer to individual Series
2011-08-21 | E-GEOD-30568 | biostudies-arrayexpress
Project description:Elexacaftor/tezacaftor/ivacaftor (ETI) CFTR modulator therapy has led to rapid and substantial improvements in cystic fibrosis (CF) airway disease. Underlying molecular and cellular mechanisms, long-term efficacy, and ability to reverse airway epithelial remodeling in established disease remain unclear. Longitudinal nasal brushes from an adult CF cohort were used to evaluate gene expression, cellular composition, stem cell function, and microbiome changes at baseline and at six months and two years after ETI. The baseline to six month span showed a massive downregulation of extensive neutrophilic inflammatory gene expression programs that correlated with increased pulmonary function and decreased sinusitis. Primary airway epithelial stem cell cultures from matched donor samples showed partially improved differentiation and barrier capacity at six months. Although clinical outcomes remained stable during the six month to two year span, transcriptional changes revealed a resurgence of baseline inflammatory programs. Time course gene expression was consistent with ongoing normalization of epithelial remodeling. Relative abundance of Pseudomonas also decreased during the time course. These data suggest that ETI rectifies inflammation, epithelial remodeling, and bacterial infection in the airways, but resurgence of inflammatory gene expression may indicate ongoing inflammation, potentially presaging disease progression with long-term therapy.
2025-09-03 | GSE306517 | GEO
Project description:We did bulk RNA sequencing in newborn cystic fibrosis (CF) and non-CF pig kidney. We compared kidney gene expression profiling between non-CF and CF pigs. RNA sequencing results showed that there is not significant difference between non-CF and CF in terms of gene expression, suggesting that CFTR knockout does not affect kidney development in newborn pigs.
2024-06-07 | GSE217122 | GEO
Project description:We have compared gene expression in human nasal brushing cells from 19 cystic fibrosis (CF) patients and 19 healthy controls using a 5.2K cDNA microarray. Our aim is to identify new disease biomarkers for the Cystic Fibrosis Gene Therapy Consortium. These markers will be used to report more effectively on the response to the administration of gene therapy in vivo. Cystic Fibrosis is a recessive genetic disease caused by mutations in the cystic fibrosis conductance regulator (CFTR) gene which encodes a chloride ion channel. The most common mutation is the ∆F508 mutation, present on 70% of CF chromosomes in Caucasian populations. The disease affects many organs in the body such as the pancreas, liver, sweat glands, small intestine and reproductive tracts but is most commonly associated with progressive, inflammatory lung disease. The current average life expectancy of CF patients is 35 years. Gene therapy is being developed as a treatment for CF airway disease, however, means of measuring the efficiency and efficacy of gene therapy in vivo are lacking. This is mainly due to the difficulty in measuring the chloride conductance of CFTR in cells and tissues. Furthermore, clinical assays for measuring improvements in lung function are insensitive. Surrogate markers of inflammation and CFTR function will therefore be important for the effective assessment of gene therapy in vivo. We have analysed gene expression in human nasal epithelium as this is considered an accessible surrogate for the conducting airways where disease manifests in the majority of patients. Additionally, this tissue will be sampled in clinical trials.
2011-04-30 | E-MEXP-436 | biostudies-arrayexpress
Project description:THE RESPIRATORY MICROBIOME IN CYSTIC FIBROSIS: COMPARTMENT PATTERNS AND CLINICAL RELATIONSHIPS
| PRJEB31332 | ENA
Project description:Cystic Fibrosis (CF) is associated with pathology in multiple tissues including the lung, digestive tract and reproductive system. Lung disease is primarily a post-natal event but other organs are affected before birth. Here we use the CF sheep model to investigate the initiation and progression of CF disease through gestation.
2023-02-14 | GSE202024 | GEO
Project description:Elexacaftor/tezacaftor/ivacaftor (ETI, Trikafta) is highly effective treatment for many cystic fibrosis patients, at least partly because it increases CFTR mediated Cl- and HCO3- secretion by airway epithelial cells leading to improved lung function and less frequent exacerbations and hospitalizations. However, little is known about how ETI affects airway epithelial cells in ways not related to CFTR mediated Cl- and HCO3- secretion, for example how ETI affects the expression of genes other than CFTR or how ETI might affect airway cells’ response to infection. It is established that CF airway cells bearing the delta F 508 mutation the CFTR gene respond characteristically differently from wild type CFTR cells, and we hypothesized that, as a highly effective CFTR modulator, ETI might make airway cells from CF donors respond to pathogen stimulation (Pseudomonas aeruginosa PA14 or outer membrane vesicles isolated from these bacteria) in more the same way that cells from wild type, healthy control cells do. We tested this hypothesis by measuring gene expression responses in polarized primary CF airway cells exposed to ETI alone or ETI in the presence of a pathogen challenge (PA14 or outer membrane vesicles). Responses of CFTR wild type primary CF airway cells to PA14 or outer membrane vesicles was also measured for comparison
2024-06-25 | GSE268718 | GEO