poFUT1 promotes uterine angiogenesis and vascular remodeling via enhancing the O-fucosylation on uPA
poFUT1 promotes uterine angiogenesis and vascular remodeling via enhancing the O-fucosylation on uPA
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poFUT1通过增强uPA上的O-岩藻糖基化促进子宫血管生成和血管重塑
DOI：
10.1038/s41419-019-2005-3
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发表时间：
2019
影响因子：
9
通讯作者：
Yan Qiu
中科院分区：
文献类型：
--
作者：
Zhang D;an;Yang Yu;Liang Caixia;Liu Jianwei;Wang Hao;Liu Shuai;Yan Qiu
子宫血管生成和血管重塑在决定正常月经周期和成功妊娠中起着关键作用。子宫血管生成不良通常导致妊娠失败。蛋白O-聚焦转移酶1 （poFUT1）是负责糖蛋白上O-聚焦聚糖生物合成的关键酶。然而，poFUT1在子宫血管生成和血管重构中的动态表达和调控尚不清楚。我们发现，月经周期子宫内膜分泌期血管腔的扩张大于增生期；而与健康孕妇相比，流产患者蜕膜血管腔窄，血管少。此外，与增殖期相比，poFUT1在子宫内膜分泌期表达升高，而在流产患者子宫中表达低于健康孕妇。通过hESCs和小鼠模型，我们证明了poFUT1增加了uPA上的O-聚焦，激活了RhoA信号通路，从而促进了子宫血管生成和血管重塑。我们还提供证据表明，poFUT1通过降低hESCs的干性来促进hESCs的血管生成。这些发现揭示了对子宫血管生成和血管重构的新认识。该研究表明，poFUT1可被视为一种新的潜在的流产诊断和治疗靶点。
Uterine angiogenesis and vascular remodeling play critical roles in determing the normal menstrual cycle and successful pregnancy. Poor uterine angiogenesis usually results in pregnancy failure. Protein O-fucosyltransferase 1 (poFUT1) is the key enzyme responsible for O-fucosylated glycan biosynthesis on glycoproteins. However, the dynamic expression and regulation of poFUT1 on the uterine angiogenesis and vascular remodeling remain unknown. Here, we showed that the enlargement of the vascular lumen in the secretory phase was greater than that in the proliferative phase of the uterine endometrium during menstrual cycle; whereas there was a narrower vessel lumen and fewer blood vessels in the decidua from miscarriage patients than in that from healthy pregnancy women. Additionally, the expression of poFUT1 was increased in the uterine endometrium during the secretory phase compared with that in the proliferation phase, and its expression was decreased in the uterus of miscarriage patients compared with that of the healthy pregnancy women. Using hESCs and a mouse model, we demonstrated that poFUT1 increased the O-fucosylation on uPA, and activated of the RhoA signaling pathway, thus facilitating uterine angiogenesis and vascular remodeling. We also provide evidence that poFUT1 promotes hESCs angiogenesis by the decreased stemness of hESCs. These findings reveal a new insight into the uterine angiogenesis and vascular remodeling. The study suggests that poFUT1 could be seen as a novel potential diagnostic and therapeutic target for miscarriage.