Endoplasmic reticulum stress transducer OASIS promotes terminal differentiation of goblet cells in large intestine

Abstract

OASIS is a transmembrane transcription factor which is localized at endoplasmic reticulum, and is cleaved at membrane region in response to ER stress. OASIS is expressed in bones, intestine and astrocyte in central nervous system. Among these, the most intense signals are detected in large intestine. In situ hybridization showed OASIS strongly expressed in pre‐goblet cells at crypt base of large intestine. In 3‐weeks‐old Oasis−/− mice, the expression of Mucin2, a mature goblet cell marker, was lower, and that of Trefoil factor 3, a pre‐goblet cell marker, was higher than in those of wild‐type mice. Electron microscope analysis showed abnormal morphology of mucus vesicles in the goblet cells of Oasis−/− mice, indicating that OASIS is essential for normal formation of mucus vesicle. We further examined the roles of OASIS in goblet cell differentiation using LS174T colon cancer cells. The expression of OASIS was up‐regulated, and the cleavage of OASIS at the membrane region was accelerated during differentiation of LS174T to mature goblet cells. Knockdown of OASIS transcript resulted in disturbance of goblet cell terminal differentiation. Taken together, OASIS could play crucial roles in accelerating terminal differentiation of goblet cells in large intestine involving formation of mucus vesicles.