Increased susceptibility to dextran sulfate sodium-induced colitis in the endoplasmic reticulum stress transducer OASIS deficient mice.
OASIS is a basic leucine zipper (bZIP) transmembrane transcription factor that is activated in response to endoplasmic reticulum (ER) stress. Previously, we showed that OASIS regulates final maturation of goblet cells in the large intestine. In the present study, to elucidate the roles of OASIS under pathophysiological conditions, we examined the stress response and inflammatory responses in Oasis deficient (Oasis⁻/⁻) mice exposed to dextran sulfate sodium (DSS) to induce colitis. A significant loss of body weight and an increase of mortality were observed in Oasis⁻/⁻ mice with DSS-induced colitis compared with those in WT mice. The mucosa of the large intestine in Oasis⁻/⁻ mice exhibited severe damage involving inflammatory cell infiltration. The expression levels of ER stress and apoptosis markers in intestinal epithelial cells were upregulated in Oasis⁻/⁻ mice. These abnormalities were improved by treatment with tauroursodeoxycholic acid, a chemical chaperone that facilitates protein folding. Taken together, our findings demonstrate that OASIS plays important roles in protection of the large intestinal mucosa in DSS-induced colitis through attenuation of ER stress and inflammation.
Department of Biochemistry, Institute of Biomedical & Health Sciences, University of Hiroshima, 1-2-3 Kasumi, Minami-ku, Hiroshima, Japan.
Kenta
K
Hino
Department of Biochemistry, Institute of Biomedical & Health Sciences, University of Hiroshima, 1-2-3 Kasumi, Minami-ku, Hiroshima, Japan.
Atsushi
A
Saito
Department of Biochemistry, Institute of Biomedical & Health Sciences, University of Hiroshima, 1-2-3 Kasumi, Minami-ku, Hiroshima, Japan.
Rie
R
Asada
Department of Biochemistry, Institute of Biomedical & Health Sciences, University of Hiroshima, 1-2-3 Kasumi, Minami-ku, Hiroshima, Japan.
Soshi
S
Kanemoto
Department of Biochemistry, Institute of Biomedical & Health Sciences, University of Hiroshima, 1-2-3 Kasumi, Minami-ku, Hiroshima, Japan.
Kazunori
K
Imaizumi
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D049109:Cell Proliferation; D002478:Cells, Cultured; D003092:Colitis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D017362:Cyclic AMP Response Element-Binding Protein / Q000502:physiology*; D016264:Dextran Sulfate / Q000633:toxicity*; D004198:Disease Susceptibility; D059865:Endoplasmic Reticulum Stress; D005260:Female; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D007249:Inflammation / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects / Q000473:pathology; D008156:Luciferases / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
C119923:Creb3l1 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D016264:Dextran Sulfate; D008156:Luciferases