One of the features of ulcerative colitis (UC) is a defect in the protective mucus layer. This has been attributed to a reduced number of goblet cells (GC). However, it is not known whether abnormal GC mucus secretion also contributes to the reduced mucus layer. Our aims were to investigate whether GC secretion was abnormal in UC and exists as a long-term effect of chronic inflammation.
Colonoids were established from intestinal stem cells of healthy subjects (HS) and patients with UC. Colonoids were maintained as undifferentiated (UD) or induced to differentiate (DF) and studied as 3D or monolayers on Transwell filters. Total RNA was extracted for quantitative real-time PCR analysis. Carbachol and PGE2 mediated mucin stimulation was examined by MUC2 IF/confocal microscopy and TEM.
Colonoids from UC patients can be propagated over many passages; however, they exhibit a reduced rate of growth and TEER compared with HS. Differentiated UC colonoid monolayers form a thin and non-continuous mucus layer. UC colonoids have increased expression of secretory lineage markers: ATOH1 and SPDEF, along with MUC2 positive GCs but failed to secrete mucin in response to the cholinergic agonist carbachol and PGE2, which caused increased secretion in HS. Exposure to TNF-α (5days), reduced the number of GC with a greater percentage decrease in UC colonoids compared to HS.
Chronic inflammation in UC causes long-term changes in GC, leading to abnormal mucus secretion. This continued defect in GC mucus secretion may contribute to the recurrence in UC.

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