Shindo Ryodai, Katagiri Takaharu, Komazawa-Sakon Sachiko, Ohmuraya Masaki, Takeda Wakami, Nakagawa Yoshiko, Nakagata Naomi, Sakuma Tetsushi, Yamamoto Takashi, Nishiyama Chiharu, Nishina Takashi, Yamazaki Soh, Kameda Hideto, Nakano Hiroyasu
Department of Biochemistry, Toho University Graduate School Medicine, 5-21-16 Omori-Nishi, Ota-ku, Tokyo, 143-8540, Japan.
Division of Rheumatology, Department of Internal Medicine, Ohashi Medical Center, 2-22-36 Ohashi, Meguro-ku, Tokyo, 153-8515, Japan.
Biochem Biophys Rep. 2020 Feb 7;21:100738. doi: 10.1016/j.bbrep.2020.100738. eCollection 2020 Mar.
Regenerating islet-derived protein (Reg)3β belongs to a member of the Reg family of proteins and has pleiotropic functions, including antimicrobial activity and tissue repair. However, whether Reg3β plays a protective role in the development of colitis and ileitis has not been fully investigated. We generated transgenic mice expressing a short form of cellular FLICE-inhibitory protein (cFLIPs) that promotes necroptosis, a regulated form of cell death. cFLIPs transgenic ( Tg) mice develop severe ileitis in utero. Although Reg3β is undetectable in the small intestine of wild-type embryos, its expression is aberrantly elevated in the small intestine of Tg embryos. To test whether elevated Reg3β attenuates or exacerbates ileitis in Tg mice, we generated a strain. mice grew to adulthood without apparent abnormalities. Deletion of in Tg mice exacerbated the embryonic lethality of Tg mice. Dextran sulfate sodium-induced colitis, characterized by body weight loss and infiltration of neutrophils, was exacerbated in compared to wild-type mice. Moreover, the expression of , an inflammatory cytokine and , a marker for tissue repair macrophages was elevated in the colon of mice compared to wild-type mice after DSS treatment. Together, these results suggest that attenuation of colitis and ileitis is a result of Reg3β's real function.
再生胰岛衍生蛋白（Reg）3β属于Reg蛋白家族成员，具有多种功能，包括抗菌活性和组织修复。然而，Reg3β在结肠炎和回肠炎发展过程中是否发挥保护作用尚未得到充分研究。我们构建了表达促进坏死性凋亡（一种程序性细胞死亡形式）的短型细胞FLICE抑制蛋白（cFLIPs）的转基因小鼠。cFLIPs转基因（Tg）小鼠在子宫内就会发生严重的回肠炎。虽然在野生型胚胎的小肠中检测不到Reg3β，但其在Tg胚胎的小肠中异常高表达。为了测试升高的Reg3β是否减轻或加重Tg小鼠的回肠炎，我们构建了一个缺失Reg3β的品系。缺失Reg3β的小鼠成年后没有明显异常。在Tg小鼠中缺失Reg3β会加剧Tg小鼠的胚胎致死率。与野生型小鼠相比，葡聚糖硫酸钠诱导的以体重减轻和中性粒细胞浸润为特征的结肠炎在缺失Reg3β的小鼠中更加严重。此外，在葡聚糖硫酸钠处理后，与野生型小鼠相比，缺失Reg3β的小鼠结肠中炎症细胞因子白细胞介素-1β和组织修复巨噬细胞标志物F4/80的表达升高。总之，这些结果表明结肠炎和回肠炎的减轻是Reg3β真实功能的结果。
