miR-263a Regulates ENaC to Maintain Osmotic and Intestinal Stem Cell Homeostasis in Drosophila

Publication date: Available online 22 December 2016
Source:Developmental Cell
Author(s): Kevin Kim, Ruei-Jiun Hung, Norbert Perrimon
Proper regulation of osmotic balance and response to tissue damage is crucial in maintaining intestinal stem cell (ISC) homeostasis. We found that Drosophila miR-263a downregulates the expression of epithelial sodium channel (ENaC) subunits in enterocytes (ECs) to maintain osmotic and ISC homeostasis. In the absence of miR-263a, the intraluminal surface of the intestine displays dehydration-like phenotypes, Na⁺ levels are increased in ECs, stress pathways are activated in ECs, and ISCs overproliferate. Furthermore, miR-263a mutants have increased bacterial load and expression of antimicrobial peptides. Strikingly, these phenotypes are reminiscent of the pathophysiology of cystic fibrosis (CF) in which loss-of-function mutations in the chloride channel CF transmembrane conductance regulator can elevate the activity of ENaC, suggesting that Drosophila could be used as a model for CF. Finally, we provide evidence that overexpression of miR-183, the human ortholog of miR-263a, can also directly target the expressions of all three subunits of human ENaC.

Graphical abstract

Teaser

Kim et al. demonstrate that miR-263a regulates the expression of the epithelial sodium channel ENaC to maintain osmotic and intestinal stem cell homeostasis. Furthermore, miR-263a mutants display phenotypes that are reminiscent of the pathophysiology of cystic fibrosis, suggesting that Drosophila could be used as a model for cystic fibrosis.


http://ift.tt/2hPmVhX