Irisin promotes intestinal epithelial cell proliferation via Wnt/β-Catenin and focal adhesion kinase signaling pathways

The regeneration of epithelia is crucial for maintaining intestinal homeostasis. Irisin is exercise-induced hormone that was originally found to be secreted by skeletal muscles and which regulates energy metabolism. Recent studies have revealed that irisin protects against gut inflammation. However, the direct effects of irisin on intestinal epithelial cell remains to be elucidated. In this study, mouse intestinal organoids were used to assess the effects of irisin on the proliferation of intestinal epithelial cells. The size and budding morphologies of organoids were studied by confocal microscopy. Gene expression levels were assessed by quantitative real-time PCR and Western blotting. The cell surface expressions of integrins were determined by immunofluorescent cytometry. Irisin markedly stimulated the growth of intestinal organoids, thereby increasing the surface areas and budding phenotypes of the organoids. Interestingly, irisin significantly increased the expression of both β-catenin and the transcriptional targets of Wnt signaling Lgr5 and Cyclin D1. Furthermore, irisin induced the activation of focal adhesion kinase (FAK) signaling, whereas a FAK inhibitor suppressed the cell proliferation. Taken together, irisin promotes epithelial cell proliferation via Wnt/β-Catenin and FAK signaling pathways in intestinal organoids, suggesting that irisin may be a promising therapeutic for intestinal epithelial regeneration.