Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin, China.
Mediators Inflamm. 2019 Nov 6;2019:7859460. doi: 10.1155/2019/7859460. eCollection 2019.
Reg (regenerating gene) family proteins are known to be overexpressed in gastrointestinal (GI) tissues under conditions of inflammation. However, the pathophysiological significance of Reg family protein overexpression and its regulation is still unclear. In the present study, we investigated the profile of family gene expression in a colitis model and focused on the regulation of Reg III and III, which are overexpressed in inflamed colonic mucosa. C57BL/6 mice were administered 2% dextran sulfate sodium (DSS) in drinking water for five days, and their colonic tissues were investigated histopathologically at interval for up to 12 weeks. Gene expression of the family and cytokines (, , and ) was evaluated by real-time RT-PCR, and Reg III/ expression was examined by immunohistochemistry. The effects of cytokines on STAT3 phosphorylation and HIP/PAP (type III REG) expression in Caco2 and HCT116 cells were examined by Western blot analysis. Among family genes, and were alternatively overexpressed in the colonic tissues of mice with DSS-induced colitis. The expression of STAT3-associated (, , and ) was also significantly increased in those tissues, being significantly correlated with that of . STAT3 phosphorylation and HIP/PAP expression were significantly enhanced in Caco2 cells upon stimulation with IL-6, IL-17, and IL-22. In HCT116 cells, those enhancements were also observed by IL-6 and IL-22 stimulations but not IL-17. The link between type III Reg and STAT3-associated cytokines appears to play a pivotal role in the pathophysiology of DSS-induced colitis.
Reg 家族蛋白已知在炎症条件下胃肠道 (GI) 组织中过度表达。然而，Reg 家族蛋白过度表达的病理生理意义及其调控仍不清楚。在本研究中，我们研究了结肠炎模型中 家族基因表达谱，并重点研究了在炎症性结肠黏膜中过度表达的 Reg III 和 III 的调控。C57BL/6 小鼠饮用 2%葡聚糖硫酸钠 (DSS) 5 天，在长达 12 周的时间内每隔一段时间对其结肠组织进行组织病理学检查。通过实时 RT-PCR 评估 家族和细胞因子（、、和）的基因表达，并通过免疫组织化学检查 Reg III/表达。通过 Western blot 分析研究细胞因子对 Caco2 和 HCT116 细胞中 STAT3 磷酸化和 HIP/PAP（III 型 REG）表达的影响。在 DSS 诱导的结肠炎小鼠的结肠组织中， 家族基因中 和 交替过度表达。这些组织中 STAT3 相关的 （、、和）的表达也显著增加，与 的表达显著相关。IL-6、IL-17 和 IL-22 刺激可显著增强 Caco2 细胞中 STAT3 磷酸化和 HIP/PAP 表达。在 HCT116 细胞中，IL-6 和 IL-22 刺激也观察到这些增强，但 IL-17 没有。III 型 Reg 与 STAT3 相关细胞因子之间的联系似乎在 DSS 诱导的结肠炎的病理生理学中发挥关键作用。
