Versican provides the provisional matrix for uterine spiral artery dilation and fetal growth

Versican provides the provisional matrix for uterine spiral artery dilation and fetal growth
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Versican 为子宫螺旋动脉扩张和胎儿生长提供临时基质

DOI:
10.1016/j.matbio.2022.11.004
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发表时间:
2023
期刊:
影响因子:
6.9
通讯作者:
Mandai Masaki
Mandai Masaki
中科院分区:
生物学1区
文献类型:
--
作者:
Sagae Yusuke;Horie Akihito;Yanai Akihiro;Ohara Tsutomu;Nakakita Baku;Kitawaki Yoshimi;Okunomiya Asuka;Tani Hirohiko;Yamaguchi Ken;Hamanishi Junzo;Lydon John P.;Daikoku Takiko;Watanabe Hideto;Mandai Masaki

文献摘要

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子宫内膜中的细胞外基质(ECM)在哺乳动物妊娠中起着至关重要的作用。我们已经证明,子宫内膜上皮分泌的多功能蛋白聚糖促进胚胎着床。Versican是一种蛋白聚糖,是临时基质中的主要参与者,versikine是其被ADAMTS蛋白酶切割的N-末端片段,用作生物活性分子。在这里,由于多功能蛋白聚糖在胎盘中的表达在人类和小鼠中动态改变,我们研究了多功能蛋白聚糖在妊娠中的作用,使用子宫特异性Vcan缺失小鼠(uKO小鼠)和ADAMTS抗性多功能蛋白聚糖表达小鼠(V1 R小鼠)。uKO小鼠表现出螺旋动脉扩张不足,随后是胎儿生长受限和母体高血压。进一步分析显示螺旋动脉扩张所需的组织驻留自然杀伤细胞增殖受损。V1 R小鼠表现出与对照相同的结果,排除了versikine的参与。我们的研究结果提供了一个新的概念,多功能蛋白聚糖,ECM的一个因素,有助于胎盘形成和以下胎儿的生长。
The extracellular matrix (ECM) in the endometrium plays a crucial role in mammalian pregnancy. We have shown that versican secreted from the endometrial epithelium promotes embryo implantation. Versican is a proteoglycan, a major player in the provisional matrix, and versikine, its N-terminal fragment cleaved by ADAMTS proteinases, serves as a bioactive molecule. Here, since versican expression in the placenta was dynamically altered in humans and mice, we investigated the role of versican in pregnancy using uterine-specificVcandeletion mice (uKO mice) and ADAMTS-resistant versican expressing mice (V1R mice). uKO mice exhibited insufficient spiral artery dilation, followed by fetal growth restriction and maternal hypertension. Further analysis revealed impaired proliferation of tissue-resident natural killer cells required for spiral artery dilation. V1R mice showed the same results as the control, eliminating the involvement of versikine. Our results provide a new concept that versican, one factor of ECM, contributes to placentation and following fetal growth.