The gastrointestinal (GI) tract is the largest hormone-producing organ in the body due to a specialized cell population called enteroendocrine cells (EECs). The number of EECs increases in the mucosa of inflammatory bowel disease (IBD) patients; however, the mechanisms responsible for these changes remain unknown. Here, we show that the proinflammatory cytokines IFNγ and TNFα or DSS induced colitis increased the number of EECs producing Chromogranin A (CgA) in the colonic mucosa of C57BL/6J mice. CgA-positive cells were non-proliferating cells enriched with inactive PTEN and autophagy markers. Moreover, inhibition of Akt and autophagy prevented the increase of CgA-positive cells after IFNγ/TNFα treatment. Similarly, we observed that CgA-positive cells in the colonic mucosa of patients with colitis expressed Akt and autophagy markers. These findings suggest that Akt signaling and autophagy control differentiation of the intestinal enteroendocrine cell lineage during inflammation.
- Chromogranin A
- 14-3-3 proteins
- ©2016 The Author(s)
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