VEGF‐A regulated by progesterone governs uterine angiogenesis and vascular remodelling during pregnancy

EMBO Molecular Medicine

Minah Kim¹  Hyeung Ju Park¹  Jae Won Seol¹  Jeon Yeob Jang¹  Young-Suk Cho¹  Kyu Rae Kim²  Youngsok Choi⁵  John P. Lydon⁷  Francesco J. DeMayo⁷  Masabumi Shibuya³  Napoleone Ferrara⁶  Hoon-Ki Sung⁸  Andras Nagy⁸  Kari Alitalo⁴ 

[1] Laboratory of Vascular Biology and Stem Cells and Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea;Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea;Institute of Physiology and Medicine, Jobu University, Gunma, Japan;Molecular/Cancer Biology Laboratory, Institute for Molecular Medicine, University of Helsinki, Helsinki, Finland;Department of Biomedical Science, CHA University, Seoul, Korea;Moores Cancer Center, University of California San Diego, La Jolla, CA, USA;Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA;Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada

关键词: decidual angiogenesis;    pregnant uterus;    vascular sinus folding;    vascular regression;    VEGF‐A;   

DOI  :  10.1002/emmm.201302618

来源: Wiley

【 摘 要 】

Abstract

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.

【 授权许可】

CC BY   
Copyright © 2013 EMBO Molecular Medicine

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