摘要
目的探讨CXXC5在炎症性肠病中的潜在功能。方法利用葡聚糖硫酸钠(DSS)诱导的小鼠急性溃疡性结肠炎模型检测野生型对照小鼠和CXXC5基因敲除小鼠对DSS的敏感性,利用免疫组织化学染色、实时荧光定量PCR和免疫印迹法分别检测了肠道上皮细胞增殖、炎症因子表达和细胞增殖相关通路的激活。结果发现CXXC5基因敲除小鼠比野生型对照小鼠更敏感,呈现严重的肠道组织损伤和高致死率。我们进一步发现CXXC5基因敲除小鼠的肠上皮细胞增殖在修复期非常低,而对照小鼠的肠上皮细胞则大量增殖。虽然炎症因子的表达在2组小鼠中相当,但是我们发现c-MYC蛋白在CXXC5基因敲除小鼠的肠上皮细胞中表达量明显偏低,这可能导致了细胞增殖的减少。结论证明CXXC5能够抑制炎症性肠病的发生,促进肠上皮细胞的损伤修复,因此是控制肠炎发生的一个重要调控子。
Zinc-finger CXXC protein 5 (CXXC5) has been reported to play important roles in viral infection and tissue remodeling, but its function in inflammatory bowel diseases remains unknown. The aim of this study is to investigate the role of CXXC5 in ulcerative colitis. Oral administration of dextran sulfate sodium (DSS) was used as an inducer of ulcerative colitis in wild-type and CXXCS-knockout mice. The results showed that compared with control mice, CXXC5 knockout mice were more sensitive to DSS-induced colitis, exhibiting higher mortality and stronger intestinal tissue injury. Immunohistochemistry, real-time PCR and Western blot were performed to examine cell proliferation, inflammatory genes expression and pathways associating with cell proliferation, respectively. While the intestinal epithelial cells (IECs) of wild-type mice proliferated rapidly in the repair phase after DSS treatment, while the proliferation of CXXCS-deficient IECs were blunted. Mechanistically, the expression of c-MYC was much lower in the IECs of CXXC5-knockout mice, which might contributed to the abrogated cell proliferation. Together, our study uncovers CXXC5 as an important regulator of cell proliferation and injury repair, thereby controlling colitis.
作者
郝从芳
谢亚栋
马世鑫
杜东书
肖晖
HAO Congfang;XIE Yadong;MA Shixin;DU Dongshu;XIAO Hui(School of Life Sciences,Shanghai University,Shanghai 200444,China;Institute Pasteur of Shanghai,Chinese Academy of Sciences,Shanghai 200031,China)
出处
《免疫学杂志》
CAS
CSCD
北大核心
2018年第8期674-682,共9页
Immunological Journal
基金
国家自然科学基金(81720108019)
关键词
锌脂蛋白CXXC5
肠炎
肠上皮细胞
细胞增殖
Zinc-finger CXXC protein 5
Ulcerative colitis
Intestinal epithelial cells
Cell proliferation