title: The endoplasmic reticulum stress transducer OASIS is involved in the terminal differentiation of goblet cells in the large intestine.
abstract: OASIS is a basic leucine zipper transmembrane transcription factor localized in the endoplasmic reticulum (ER) that is cleaved in its transmembrane region in response to ER stress. This novel ER stress transducer has been demonstrated to express in osteoblasts and astrocytes and promote terminal maturation of these cells. Additionally, OASIS is highly expressed in goblet cells of the large intestine. In this study, we investigated the roles of OASIS in goblet cell differentiation in the large intestine. To analyze the functions of OASIS in goblet cells, we examined morphological changes and the expression of goblet cell differentiation markers in the large intestine of Oasis(-/-) mice. By disrupting the Oasis gene, the number of goblet cells and production of mucus were decreased in the large intestine. Oasis(-/-) goblet cells showed abnormal morphology of mucous vesicles and rough ER. The expression levels of mature goblet cell markers were lower, and conversely those of early goblet cell markers were higher in Oasis(-/-) mice, indicating that differentiation from early to mature goblet cells is impaired in Oasis(-/-) mice. To determine the association of OASIS with other factors involved in goblet cell differentiation, in vitro experiments using a cell culture model were performed. We found that OASIS was activated in response to mild ER stress that is induced in differentiating goblet cells. Knockdown of the Oasis transcript perturbed goblet cell terminal differentiation. Together, our data indicate that OASIS plays crucial roles in promoting the differentiation of early goblet cells to mature goblet cells in the large intestine.
authors.affiliation: Department of Biochemistry, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan.
authors.forename: Rie
authors.initials: R
authors.lastname: Asada
authors.forename: Atsushi
authors.initials: A
authors.lastname: Saito
authors.forename: Noritaka
authors.initials: N
authors.lastname: Kawasaki
authors.forename: Soshi
authors.initials: S
authors.lastname: Kanemoto
authors.forename: Hideo
authors.initials: H
authors.lastname: Iwamoto
authors.forename: Mami
authors.initials: M
authors.lastname: Oki
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Miyagi
authors.forename: Soutarou
authors.initials: S
authors.lastname: Izumi
authors.forename: Kazunori
authors.initials: K
authors.lastname: Imaizumi
mesh_terms: D000818:Animals; D000943:Antigens, Differentiation / Q000096:biosynthesis; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism*; D059865:Endoplasmic Reticulum Stress / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology; D020397:Goblet Cells / Q000166:cytology / Q000378:metabolism*; D007420:Intestine, Large / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D000943:Antigens, Differentiation; C119923:Creb3l1 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D009419:Nerve Tissue Proteins