Cholinergic signaling modulates intestinal pathophysiology in a drosophila model of cystic fibrosis - PubMed
4 days ago
- #Cystic Fibrosis
- #Drosophila Model
- #Cholinergic Signaling
- Cystic fibrosis (CF) is caused by mutations in the CFTR chloride/bicarbonate channel, affecting epithelial cells.
- Current CF therapies focus on restoring CFTR function, but gut-related pathologies often persist.
- Drosophila melanogaster was used as a model to study gut-specific effects of Cftr loss.
- Enterocyte-specific knockdown of Cftr in flies mimics CF pathologies like reduced motility and malabsorption.
- Single-nuclei RNA sequencing revealed upregulation of acetylcholine esterase (Ace), reducing cholinergic signaling.
- Cholinergic signaling is diminished in CF guts, and restoring it via Ace knockdown rescues CF phenotypes.
- The transcription factor Fork head (Fkh) regulates Ace expression in CF guts.
- Enhancing cholinergic signaling may be a therapeutic strategy for CF gastrointestinal symptoms.