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[摘要]：An understanding of the signaling mechanism(s) that regulate the differential expression of gastric mucin MUC5AC in colonic epithelial cells would contribute significantly to investigations of its role in colonic mucosa infected with the bacterial pathogen Shigella dysenteriae. Here we show that S. dysenteriae-induced expression of interleukin-1 beta upregulates MUC2 expression and the differential expression of MUC5AC. Differential expression of MUC5AC involves crosstalk between interleukin-1 beta and Akt, whereby the trefoil factor family peptide TFF3 activates Akt by phosphorylation of EGFR. TFF3 also downregulates E-cadherin expression, causing accumulation of beta-catenin in the cytosol. Phosphorylation of GSK-3 beta (inactivated) by activated Akt inhibits ubiquitylation of beta-catenin, leading to its nuclear translocation, which then induces the expression of MUC5AC and cyclin D1. Accumulation of cyclin D1 alters the cell cycle, promoting cell survival and proliferation. Human colon HT29MTX cells, which overexpress MUC5AC, were resistant to adherence and invasion of S. dysenteriae when compared with other mucin-secreting HT29 cell types. Thus, during infection with S. dysenteriae, crosstalk between interleukin-1 beta and Akt wired by TFF3 induces expression of MUC5AC: in colonic epithelial cells. Differentially expressed gastric MUC5AC aids in mucosal clearance of S. dysenteriae, inhibiting adherence and invasion of the pathogen to colonic epithelial cells, which protects the host. |
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