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Progesterone receptor in the vascular endothelium triggers physiological uterine permeability preimplantation.
Goddard, Lauren M; Murphy, Thomas J; Org, Tönis; Enciso, Josephine M; Hashimoto-Partyka, Minako K; Warren, Carmen M; Domigan, Courtney K; McDonald, Austin I; He, Huanhuan; Sanchez, Lauren A; Allen, Nancy C; Orsenigo, Fabrizio; Chao, Lily C; Dejana, Elisabetta; Tontonoz, Peter; Mikkola, Hanna K A; Iruela-Arispe, M Luisa.
Afiliação
  • Goddard LM; Department of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Murphy TJ; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Org T; Department of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Enciso JM; Division of Neonatology, Department of Pediatrics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Hashimoto-Partyka MK; Department of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Warren CM; Department of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Domigan CK; Department of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • McDonald AI; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • He H; Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Sanchez LA; Department of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Allen NC; Department of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Orsenigo F; IFOM, Foundation FIRC Institute of Molecular Oncology, 20139 Milan, Italy.
  • Chao LC; Department of Pathology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Dejana E; IFOM, Foundation FIRC Institute of Molecular Oncology, 20139 Milan, Italy.
  • Tontonoz P; Department of Pathology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Mikkola HK; Department of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Iruela-Arispe ML; Department of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: arispe@mcdb.ucla.edu.
Cell ; 156(3): 549-62, 2014 Jan 30.
Article em En | MEDLINE | ID: mdl-24485460
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Útero / Permeabilidade Capilar / Endotélio Vascular Limite: Animals / Female / Humans Idioma: En Ano de publicação: 2014 Tipo de documento: Article
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Útero / Permeabilidade Capilar / Endotélio Vascular Limite: Animals / Female / Humans Idioma: En Ano de publicação: 2014 Tipo de documento: Article