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| Status |
Public on Jan 01, 2014 |
| Title |
Physiological Vascular Permeability Requires Induction of Endothelial NR4A1 by Progesterone Receptor [ChIP-Seq] |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
Vascular permeability is frequently associated with inflammation and it is triggered by chemokines and by a cohort of secreted permeability factors, such as VEGF. In contrast, here we showed that the physiological vascular permeability that precedes implantation is directly controlled by progesterone receptor (PR) and it is independent of VEGF. Both global and endothelial-specific deletion of PR block physiological vascular permeability in the uterus while misexpression of PR in the endothelium of other organs results in ectopic vascular leakage. Integration of genome-wide transcriptional profile of endothelium and ChIP-sequencing revealed that PR induces a NR4A1 (Nur77/TR3) specific transcriptional program that broadly regulates vascular permeability in response to progesterone. This program triggers concurrent suppression of several junctional proteins and leads to an effective, timely and venule-specific regulation of vascular barrier function. Silencing NR4A1 blocks PR-mediated permeability responses indicating a direct link between PR and NR4A1. These results reveal a previously unknown function for progesterone receptor on endothelial cell biology with consequences to physiological vascular permeability and implications to the clinical use of progestins and anti-progestins on blood vessel integrity.
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| |
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| Overall design |
Examination of PR binding sites in HUVEC cells using ChIP-seq (non-infected-negative control, PR infected followed by ligand treatment-PR+P or vehicle PR)
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| |
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| Contributor(s) |
Goddard L, Murphy TJ, Org T, Enciso JM, Hashimoto-Partyka MK, Warren CM, Sanchez LA, Allen NC, Tontonoz P, Mikkola HK, Iruela-Arispe ML |
| Citation(s) |
24485460 |
| Submission date |
Jan 27, 2013 |
| Last update date |
May 15, 2019 |
| Contact name |
Lauren Goddard |
| Organization name |
University of California-Los Angeles
|
| Department |
Molecular, Cell, and Developmental Biology
|
| Lab |
Dr. Luisa Iruela-Arispe
|
| Street address |
621 Charles E. Young Dr. S.
|
| City |
Los Angeles |
| State/province |
CA |
| ZIP/Postal code |
90095 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
|
| Samples (8)
|
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| This SubSeries is part of SuperSeries: |
| GSE43789 |
Physiological Vascular Permeability Requires Induction of Endothelial NR4A1 by Progesterone Receptor |
| GSE46503 |
Selective suppression of endothelial cytokine production by progesterone receptor |
|
| Relations |
| BioProject |
PRJNA187478 |
| SRA |
SRP018235 |
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