Cholinergic Signaling Modulates Intestinal Pathophysiology in a Drosophila Model of Cystic Fibrosis
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PROVIDER: PRJNA1281518 | ENA |
REPOSITORIES: ENA
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Project description:Cystic Fibrosis (CF) is a genetic disease caused by mutations in the CFTR gene, which affects cells in organs like the lungs, pancreas, and gut. Treatments aim to fix the CFTR protein, but many gut issues remain untreated. In this study, we use fruit flies (Drosophila) as a model to study the effects of losing CFTR specifically in the gut. We show that knocking down CFTR in gut cells leads to problems seen in CF, such as poor gut movement, trouble absorbing nutrients, and low energy levels. Using RNA sequencing, we find that CF guts have higher levels of the gene acetylcholine esterase (Ace), which lowers cholinergic (nerve signal) activity. Experiments confirm that CF guts are less sensitive to cholinergic signals, but reducing Ace brings back normal gut function. We also find a transcription factor called Forkhead (Fkh), similar to human FOXA1/2, that increases Ace in CF. Our study shows that the fruit fly gut is a useful model for studying CF in the gut, and suggests that boosting cholinergic signaling could help treat gut problems in CF.
2025-07-16 | GSE300597 | GEO
Project description:This multi-center study will compare multi-target DNA and quantitative FIT stool-based testing to colonoscopy in individuals with Cystic Fibrosis (CF) undergoing colon cancer screening with colonoscopy. The primary endpoint is detection of any adenomas, including advanced adenomas and colorectal cancer (CRC).
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Project description:Drosophila model for studying cystic fibrosis pathophysiology of the gastrointestinal system
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Project description:To identify genes relevant for cystic fibrosis pathophysiology, we profiled blood samples in CF patients and healthy controls using RNA-seq. Weighted Gene Co-expression Network Analysis of a transcriptomic dataset allowed us to identify 28 co-expressed modules that correlated with clinical traits of interest in cystic fibrosis.
2020-03-26 | GSE136371 | GEO
Project description: Not available
| S-EPMC12923121 | biostudies-literature
Project description:Our laboratory has held a long interest in the glycosylation changes seen on the surface of airway epithelia of patients with the disease cystic fibrosis (CF). Experiments from our laboratory have detailed a CF glycosylation phenotype of increased Fuca1,3/4 and decreased Fuca1,2 and sialic acid on the surfaces of immortalized and primary CF cells compared to non-CF cells. Further, we have shown that gene transfer and subsequent expression of a wild type CF plasmid in CF airway cells results in correction or reversal of this glycosylation phenotype. We hypothesize that the changes in glycosylation seen in CF cells are key in the pathophysiology of the cystic fibrosis airway disease. For example, it has been shown that Pseudomonas aeruginosa, a bacterium that has a predilection for colonizing CF airways, adheres to asialylated glycolipids and glycoconjugates with terminal Fuca1,3/4. One focus of our laboratory is to elucidate the etiology of the glycosylation changes seen in CF cells and the mechanism by which these changes are reversed by wild type CFTR gene transfer. We propose to study the gene expression of immortalized and primary CF and non-CF airway epithelial cells: 1. CF/T43 vs. BEAS-2B cells. These are two widely used immortalized airway cell lines that we have used extensively in the past. 2. C38 cells; C38 cells are IB3 cells expressing wtCFTR. The experimental focus is to elucidate the etiology of the glycosylation changes seen in Cystic Fibrosis (CF) cells and the mechanism by which these changes are reversed by wild type CFTR gene transfer. To do so, the gene expression of immortalized and primary CF and non-CF airway epithelial cells were compared and studied. Cell lines used were CF/T43 and BEAS-2B, both widely used immortalized airway cell lines. Other cell lines studied included C38 cell lines (clonal derivatives of IB3 cells expressing wtCFTR).
2011-01-07 | E-GEOD-26482 | biostudies-arrayexpress
Project description:Cystic Fibrosis (CF) is a recessively inherited disease caused by mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene. CFTR has a pivotal role in the onset of CF, and several proteins are directly or indirectly involved in its homeostasis. To study these CFTR interactors at protein species level, we used a functional proteomics approach combining 2D-DIGE, mass spectrometry and enrichment analysis. A human cystic fibrosis bronchial epithelial cell line (CFBE41o-) was used for analysis. 74 differentially expressed spots were identified and some were validated by western-blot. Enrichment analysis highlighted molecular pathways in which ezrin, HSP70, endoplasmin and lamin A/C, in addition to CFTR, were considered central hubs in CFTR homeostasis. These proteins acquire different functions through post-translational modifications, emphasizing the importance of studying the CF proteome at protein species level. Moreover, serpin H1, prelamin A/C, protein-SET and cystatin-B were associated for the first time to CF, demonstrating the importance of heat shock response, cross-talk between the cytoskeleton and signal transduction, chronic inflammation and alteration of CFTR gating in the pathophysiology of the disease. These results open new perspectives for the understanding of the proteostasis network, characteristic of CF pathology, and could provide a springboard for new therapeutic strategies.
2022-03-01 | PXD006933 | Pride
Project description:Cystic fibrosis (CF) is a recessive disease caused by mutations in theCF transmembrane conductance regulator(CFTR) gene. The most common symptoms include progressive lung disease and chronic digestive conditions. CF is the first human genetic disease to benefit from having five different species of animal models. Despite the phenotypic differences among the animal models and human CF, these models have provided invaluable insight into understanding disease mechanisms at the organ-system level. Here, we identify a member of the ABCC4 family, CG5789, that has the structural and functional properties expected for encoding theDrosophilaequivalent of human CFTR, and thus refer to it asDrosophila CFTR(Dmel\CFTR). We show that knockdown ofDmel\CFTRin the adult intestine disrupts osmotic homeostasis and displays CF-like phenotypes that lead to intestinal stem cell hyperplasia. We also show that expression of wild-type humanCFTR, but not mutant variants of CFTR that prevent plasma membrane expression, rescues the mutant phenotypes ofDmel\CFTR.Furthermore, we performed RNA sequencing (RNA-Seq)-based transcriptomic analysis usingDmel\CFTRfly intestine and identified a mucin gene,Muc68D, which is required for proper intestinal barrier protection. Altogether, our findings suggest thatDrosophilacan be a powerful model organism for studying CF pathophysiology.
2023-10-26 | GSE246379 | GEO
Project description:Cystic Fibrosis Keystone Species
| PRJNA587705 | ENA
Project description:Our laboratory has held a long interest in the glycosylation changes seen on the surface of airway epithelia of patients with the disease cystic fibrosis (CF). Experiments from our laboratory have detailed a CF glycosylation phenotype of increased Fuca1,3/4 and decreased Fuca1,2 and sialic acid on the surfaces of immortalized and primary CF cells compared to non-CF cells. Further, we have shown that gene transfer and subsequent expression of a wild type CF plasmid in CF airway cells results in correction or reversal of this glycosylation phenotype. We hypothesize that the changes in glycosylation seen in CF cells are key in the pathophysiology of the cystic fibrosis airway disease. For example, it has been shown that Pseudomonas aeruginosa, a bacterium that has a predilection for colonizing CF airways, adheres to asialylated glycolipids and glycoconjugates with terminal Fuca1,3/4. One focus of our laboratory is to elucidate the etiology of the glycosylation changes seen in CF cells and the mechanism by which these changes are reversed by wild type CFTR gene transfer.
2011-01-07 | GSE26482 | GEO