Elevated adenomatous polyposis coli in goblet cells is associated with inflammation in mouse and human colon

Abstract

Adenomatous polyposis coli (APC) serves as a gatekeeper of intestinal homeostasis by promoting cellular differentiation and maintaining crypt architecture. Although appreciated as a critical colon tumour suppressor, roles for APC in disease states such as inflammation have yet to be fully delineated. This study aimed to characterize the localization of APC protein in gastrointestinal tissues from human patients with active inflammatory bowel disease and mice with dextran sodium sulfate (DSS)-induced colitis. Fluorescence immunohistochemistry revealed a subset of goblet cells with elevated Apc staining intensity in the small intestines and proximal/medial colons of mice. Upon induction of colitis with DSS, these 'APC high ' goblet cells remained in the proximal and medial colon, but now were also observed in the distal colon. This phenotype was recapitulated in humans, with APC high goblet cells observed only in the descending colons of patients with active ulcerative colitis. In cultured human colon cells derived from normal tissue, APC depletion reduced expression of mRNAs encoding the interleukin 1 (IL1) signalling pathway components IL1β and interleukin-1 receptor (IL1R), known regulators of Muc2 expression. Treating cancer cells lacking wild-type APC with IL1β, or induction of full-length APC in these cells led to increases in IL1R and MUC2 expression. Combining IL1β treatment with APC induction led to an increase of MUC2 expression greater than expected for additive affects, suggesting that APC sensitizes cells to IL1 signalling. These findings suggest that APC has novel roles in maintaining proper goblet cell function, thus providing further evidence for APC as an important factor in intestinal tissue homeostasis and disease.

Application Prospect of Induced Pluripotent Stem Cells in Organoids and Cell Therapy

“…With the change of modern lifestyle, the incidence of colitis has gradually increased, and the prone population is very wide, difficult to cure, and the cancer rate is high, so it’s listed as one of the modern difficult diseases by the World Health Organization [ 91 ]. Long-term colitis and adenomatous polyposis can lead to contractions, perforations, and even bowel cancer [ 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 , 100 ]. Colon cancer organoids can be derived based on iPSC technology [ 101 ].…”