Liu Chang, Liang Xiaohua, Wang Jiao, Zheng Qin, Zhao Yue, Khan Muhammad Noman, Liu Shuai, Yan Qiu
Institute of Anaesthesia, Peking University Third Hospital, 49 North Garden Road, Haidian District, Beijing 100191, People's Republic of China; Department of Biochemistry and Molecular Biology, Dalian Medical University, Liaoning Provincial Core Lab of Glycobiology and Glycoengineering, Dalian 116044, People's Republic of China.
Dalian Blood Center, Dalian 116001, People's Republic of China.
Biomed Pharmacother. 2017 Apr;88:95-101. doi: 10.1016/j.biopha.2017.01.026. Epub 2017 Jan 16.
Protein O-fucosylation is an important glycosylation modification and plays an important role in embryonic development. Protein O-fucosyltransferase 1 (poFUT1) is an essential enzyme that catalyzes the synthesis of protein O-fucosylation. Our previous studies showed that poFUT1 promoted trophoblast cell migration and invasion at the fetal-maternal interface, but the role of poFUT1 in trophoblast cells proliferation remains unclear. Here, immunohistochemistry data showed that poFUT1 and PCNA levels were decreased in abortion patient's trophoblasts compared with women with normal pregnancies. Our results also showed that poFUT1 promoted trophoblast cell proliferation by CCK-8 assay and cell cycle analysis. PoFUT1 increased the phosphorylation of ERK1/2, p38 MAPK, and PI3K/Akt, while inhibitors of ERK1/2(PD98059), p38 MAPK(SB203580), and PI3K (LY294002) prevented ERK1/2, p38 MAPK, and Akt phosphorylation. Moreover, poFUT1 stimulation of trophoblast cells proliferation correlated with increased cell cycle progression by promoting cells into S-phase. The underlying mechanism involved increased cyclin D1, cyclin E, CDK 2, CDK 4, and pRb expression and decreased levels of the cyclin-dependent kinase inhibitors p21 and p27, which were blocked by inhibitors of the upstream signaling molecules MAPK and PI3K/Akt. In conclusion, poFUT1 promotes trophoblast cell proliferation by activating MAPK and PI3K/Akt signaling pathways.
蛋白质O-岩藻糖基化是一种重要的糖基化修饰，在胚胎发育中起重要作用。蛋白质O-岩藻糖基转移酶1（poFUT1）是催化蛋白质O-岩藻糖基化合成的关键酶。我们之前的研究表明，poFUT1在胎儿-母体界面促进滋养层细胞迁移和侵袭，但poFUT1在滋养层细胞增殖中的作用仍不清楚。在这里，免疫组织化学数据显示，与正常妊娠女性相比，流产患者滋养层细胞中poFUT1和PCNA水平降低。我们的结果还表明，通过CCK-8检测和细胞周期分析，poFUT促进滋养层细胞增殖。PoFUT1增加ERK1/2、p38 MAPK和PI3K/Akt的磷酸化，而ERK1/2抑制剂（PD98059）、p38 MAPK抑制剂（SB203580）和PI3K抑制剂（LY29,4002）可阻止ERK1/2、p38 MAPK和Akt的磷酸化。此外，poFUT1刺激滋养层细胞增殖与通过促进细胞进入S期增加细胞周期进程相关。潜在机制包括细胞周期蛋白D1、细胞周期蛋白E、CDK 2、CDK 4和pRb表达增加以及细胞周期蛋白依赖性激酶抑制剂p21和p27水平降低，而上游信号分子MAPK和PI3K/Akt的抑制剂可阻断这些变化。总之，poFUT1通过激活MAPK和PI3K/Akt信号通路促进滋养层细胞增殖。
