title: miR-263a Regulates ENaC to Maintain Osmotic and Intestinal Stem Cell Homeostasis in Drosophila.
abstract: 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.
authors.affiliation: Department of Genetics, Harvard Medical School, Boston, MA 02115, USA. Electronic address: kkim@genetics.med.harvard.edu.
authors.forename: Kevin
authors.initials: K
authors.lastname: Kim
authors.affiliation: Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Ruei-Jiun
authors.initials: RJ
authors.lastname: Hung
authors.affiliation: Department of Genetics, Harvard Medical School, Boston, MA 02115, USA; Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA. Electronic address: perrimon@receptor.med.harvard.edu.
authors.forename: Norbert
authors.initials: N
authors.lastname: Perrimon
mesh_terms: D000818:Animals; D058491:Bacterial Load / Q000235:genetics; D002462:Cell Membrane / Q000378:metabolism; D049109:Cell Proliferation; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism; D053503:Epithelial Sodium Channels / Q000235:genetics / Q000378:metabolism*; D004848:Epithelium / Q000378:metabolism; D005786:Gene Expression Regulation; D006706:Homeostasis / Q000235:genetics; D006863:Hydrogen-Ion Concentration; D007422:Intestines / Q000166:cytology*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D009154:Mutation / Q000235:genetics; D009995:Osmosis; D010641:Phenotype; D015398:Signal Transduction / Q000235:genetics; D012964:Sodium / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D013312:Stress, Physiological / Q000235:genetics
chemical_list: D029721:Drosophila Proteins; D053503:Epithelial Sodium Channels; C000620808:MIRN263 microRNA, Drosophila; D035683:MicroRNAs; D012964:Sodium
keywords: Drosophila; ENaC; cystic fibrosis; miR-183; miR-263a; microRNA