Progesterone receptor in the vascular endothelium triggers physiological uterine permeability preimplantation.

Abstract:

:Vascular permeability is frequently associated with inflammation and is triggered by a cohort of secreted permeability factors such as vascular endothelial growth factor (VEGF). Here, we show that the physiological vascular permeability that precedes implantation is directly controlled by progesterone receptor (PR) and is independent of VEGF. Global or endothelial-specific deletion of PR blocks physiological vascular permeability in the uterus, whereas misexpression of PR in the endothelium of other organs results in ectopic vascular leakage. Integration of an endothelial genome-wide transcriptional profile with chromatin immunoprecipitation sequencing revealed that PR induces an NR4A1 (Nur77/TR3)-dependent transcriptional program that broadly regulates vascular permeability in response to progesterone. Silencing of NR4A1 blocks PR-mediated permeability responses, indicating a direct link between PR and NR4A1. This program triggers concurrent suppression of several junctional proteins and leads to an effective, timely, and venous-specific regulation of vascular barrier function that is critical for embryo implantation.

journal_name

Cell

journal_title

Cell

authors

Goddard LM,Murphy TJ,Org T,Enciso JM,Hashimoto-Partyka MK,Warren CM,Domigan CK,McDonald AI,He H,Sanchez LA,Allen NC,Orsenigo F,Chao LC,Dejana E,Tontonoz P,Mikkola HK,Iruela-Arispe ML

doi

10.1016/j.cell.2013.12.025

subject

Has Abstract

pub_date

2014-01-30 00:00:00

pages

549-62

issue

3

eissn

0092-8674

issn

1097-4172

pii

S0092-8674(13)01594-8

journal_volume

156

pub_type

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