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MicroRNA-195 regulates Tuft cell function in the intestinal epithelium by altering translation of DCLK1
- Source :
- Am J Physiol Cell Physiol
- Publication Year :
- 2021
- Publisher :
- American Physiological Society, 2021.
-
Abstract
- Intestinal Tuft cells sense luminal contents to influence the mucosal immune response against eukaryotic infection. Paneth cells secrete antimicrobial proteins as part of the mucosal protective barrier. Defects in Tuft and Paneth cells occur commonly in various gut mucosal disorders. MicroRNA-195 (miR-195) regulates the stability and translation of target mRNAs and is involved in many aspects of cell processes and pathologies. Here, we reported the posttranscriptional mechanisms by which miR-195 regulates Tuft and Paneth cell function in the small intestinal epithelium. Mucosal tissues from intestinal epithelial tissue-specific miR-195 transgenic (miR195-Tg) mice had reduced numbers of double cortin-like kinase 1 (DCLK1)-positive (Tuft) and lysozyme-positive (Paneth) cells, compared with tissues from control mice, but there were no effects on Goblet cells and enterocytes. Intestinal organoids expressing higher miR-195 levels from miR195-Tg mice also exhibited fewer Tuft and Paneth cells. Transgenic expression of miR-195 in mice failed to alter growth of the small intestinal mucosa but increased vulnerability of the gut barrier in response to lipopolysaccharide (LPS). Studies aimed at investigating the mechanism underlying regulation of Tuft cells revealed that miR-195 directly interacted with the Dclk1 mRNA via its 3′-untranslated region and inhibited DCLK1 translation. Interestingly, the RNA-binding protein HuR competed with miR-195 for binding Dclk1 mRNA and increased DCLK1 expression. These results indicate that miR-195 suppresses the function of Tuft and Paneth cells in the small intestinal epithelium and further demonstrate that increased miR-195 disrupts Tuft cell function by inhibiting DCLK1 translation via interaction with HuR.
- Subjects :
- Male
0301 basic medicine
Lipopolysaccharide
Physiology
Transgene
Cell
Mice, Transgenic
Protein Serine-Threonine Kinases
digestive system
Cell Line
Mice
03 medical and health sciences
chemistry.chemical_compound
Doublecortin-Like Kinases
0302 clinical medicine
Immune system
Cell Line, Tumor
medicine
Animals
Humans
Secretion
Intestinal Mucosa
Chemistry
Intracellular Signaling Peptides and Proteins
Cell Biology
Intestinal epithelium
Cell biology
Mice, Inbred C57BL
Organoids
MicroRNAs
Enterocytes
HEK293 Cells
030104 developmental biology
medicine.anatomical_structure
030220 oncology & carcinogenesis
Paneth cell
Female
Goblet Cells
Caco-2 Cells
Tuft cell
Research Article
Subjects
Details
- ISSN :
- 15221563 and 03636143
- Volume :
- 320
- Database :
- OpenAIRE
- Journal :
- American Journal of Physiology-Cell Physiology
- Accession number :
- edsair.doi.dedup.....a8e51d07c32833074143ddfdbd528e4d