Increased susceptibility to dextran sulfate sodium-induced colitis in the endoplasmic reticulum stress transducer OASIS deficient mice.
Increased susceptibility to dextran sulfate sodium-induced colitis in the endoplasmic reticulum stress transducer OASIS deficient mice.
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DOI：
10.1371/journal.pone.0088048
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Imaizumi K
中科院分区：
文献类型：
--
作者：
Hino K;Saito A;Asada R;Kanemoto S;Imaizumi K
OASIS是一种碱性亮氨酸拉链（bZIP）跨膜转录因子，在内质网（ER）应激时被激活。以前，我们发现OASIS调节大肠杯状细胞的最终成熟。在本研究中，为了阐明OASIS在病理生理条件下的作用，我们研究了暴露于葡聚糖硫酸钠（DSS）以诱导结肠炎的Oasis缺陷（Oasis−/−）小鼠的应激反应和炎症反应。与WT小鼠相比，在患有DSS诱导的结肠炎的Oasis−/−小鼠中观察到体重显著减轻和死亡率增加。Oasis−/−小鼠的大肠粘膜表现出严重损伤，包括炎性细胞浸润。在Oasis−/−小鼠中，肠上皮细胞中ER应激和凋亡标志物的表达水平上调。这些异常通过牛磺熊去氧胆酸治疗得到改善，牛磺熊去氧胆酸是一种促进蛋白质折叠的化学伴侣。总之，我们的研究结果表明，OASIS通过减轻ER应激和炎症在DSS诱导的结肠炎中保护大肠粘膜中起重要作用。
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.
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