VEGF-A regulated by progesterone governs uterine angiogenesis and vascular remodelling during pregnancy.
VEGF-A regulated by progesterone governs uterine angiogenesis and vascular remodelling during pregnancy.
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DOI：
10.1002/emmm.201302618
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发表时间：
2013-09
影响因子：
11.1
通讯作者：
Koh, Gou Young
中科院分区：
文献类型：
--
作者：
Kim, Minah;Park, Hyeung Ju;Seol, Jae Won;Jang, Jeon Yeob;Cho, Young-Suk;Kim, Kyu Rae;Choi, Youngsok;Lydon, John P.;DeMayo, Francesco J.;Shibuya, Masabumi;Ferrara, Napoleone;Sung, Hoon-Ki;Nagy, Andras;Alitalo, Kari;Koh, Gou Young
妊娠期间子宫血管生成和血管重塑的特征和调节尚不清楚。在这里，我们发现，在妊娠早期（即植入后但胎盘前）快速生长的小鼠子宫中，动态和可变的蜕膜血管生成（发芽、套叠和网络化）以及活跃的剧烈血管重塑，例如“血管窦折叠”（VSF）的扩大和伸长以及壁细胞脱落，以时空方式明显发生。蜕膜血管生成主要通过表达孕酮受体（PR）的蜕膜基质细胞分泌的 VEGF-A 来调节，这些细胞主要分布在抗子宫内膜区（AMR）。相比之下，P4-PR 调节的 VEGF-A-VEGFR2 信号传导、配体独立的 VEGFR3 信号传导和子宫自然杀伤 (uNK) 细胞积极协调地调节 VSF 的增大和伸长。在产后期，Tie2信号传导可能以配体独立的方式参与子宫内膜的血管成熟，其中VEGF-A、VEGFR2和PR表达显着减少。总的来说，我们发现两种关键的血管生长因子受体——VEGFR2和Tie2——以器官型方式显着但差异性地调节子宫快速生长和退化的蜕膜血管生成和血管重塑。
The features and regulation of uterine angiogenesis and vascular remodelling during pregnancy are poorly defined. Here we show that dynamic and variable decidual angiogenesis (sprouting, intussusception and networking), and active vigorous vascular remodelling such as enlargement and elongation of ‘vascular sinus folding’ (VSF) and mural cell drop-out occur distinctly in a spatiotemporal manner in the rapidly growing mouse uterus during early pregnancy — just after implantation but before placentation. Decidual angiogenesis is mainly regulated through VEGF-A secreted from the progesterone receptor (PR)-expressing decidual stromal cells which are largely distributed in the anti-mesometrial region (AMR). In comparison, P4-PR-regulated VEGF-A-VEGFR2 signalling, ligand-independent VEGFR3 signalling and uterine natural killer (uNK) cells positively and coordinately regulate enlargement and elongation of VSF. During the postpartum period, Tie2 signalling could be involved in vascular maturation at the endometrium in a ligand-independent manner, with marked reduction of VEGF-A, VEGFR2 and PR expressions. Overall, we show that two key vascular growth factor receptors — VEGFR2 and Tie2 — strikingly but differentially regulate decidual angiogenesis and vascular remodelling in rapidly growing and regressing uteri in an organotypic manner.
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