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Lysophosphatidic acid targets vascular and oncogenic pathways via RAGE signaling
The endogenous phospholipid lysophosphatidic acid (LPA) regulates fundamental cellular processes such as proliferation, survival, motility, and invasion implicated in homeostatic and pathological conditions. Hence, delineation of the full range of molecular mechanisms by which LPA exerts its broad e...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3526353/ https://www.ncbi.nlm.nih.gov/pubmed/23209312 http://dx.doi.org/10.1084/jem.20120873 |
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author | Rai, Vivek Touré, Fatouma Chitayat, Seth Pei, Renjun Song, Fei Li, Qing Zhang, Jinghua Rosario, Rosa Ramasamy, Ravichandran Chazin, Walter J. Schmidt, Ann Marie |
author_facet | Rai, Vivek Touré, Fatouma Chitayat, Seth Pei, Renjun Song, Fei Li, Qing Zhang, Jinghua Rosario, Rosa Ramasamy, Ravichandran Chazin, Walter J. Schmidt, Ann Marie |
author_sort | Rai, Vivek |
collection | PubMed |
description | The endogenous phospholipid lysophosphatidic acid (LPA) regulates fundamental cellular processes such as proliferation, survival, motility, and invasion implicated in homeostatic and pathological conditions. Hence, delineation of the full range of molecular mechanisms by which LPA exerts its broad effects is essential. We report avid binding of LPA to the receptor for advanced glycation end products (RAGE), a member of the immunoglobulin superfamily, and mapping of the LPA binding site on this receptor. In vitro, RAGE was required for LPA-mediated signal transduction in vascular smooth muscle cells and C6 glioma cells, as well as proliferation and migration. In vivo, the administration of soluble RAGE or genetic deletion of RAGE mitigated LPA-stimulated vascular Akt signaling, autotaxin/LPA-driven phosphorylation of Akt and cyclin D1 in the mammary tissue of transgenic mice vulnerable to carcinogenesis, and ovarian tumor implantation and development. These findings identify novel roles for RAGE as a conduit for LPA signaling and suggest targeting LPA–RAGE interaction as a therapeutic strategy to modify the pathological actions of LPA. |
format | Online Article Text |
id | pubmed-3526353 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-35263532013-06-17 Lysophosphatidic acid targets vascular and oncogenic pathways via RAGE signaling Rai, Vivek Touré, Fatouma Chitayat, Seth Pei, Renjun Song, Fei Li, Qing Zhang, Jinghua Rosario, Rosa Ramasamy, Ravichandran Chazin, Walter J. Schmidt, Ann Marie J Exp Med Brief Definitive Report The endogenous phospholipid lysophosphatidic acid (LPA) regulates fundamental cellular processes such as proliferation, survival, motility, and invasion implicated in homeostatic and pathological conditions. Hence, delineation of the full range of molecular mechanisms by which LPA exerts its broad effects is essential. We report avid binding of LPA to the receptor for advanced glycation end products (RAGE), a member of the immunoglobulin superfamily, and mapping of the LPA binding site on this receptor. In vitro, RAGE was required for LPA-mediated signal transduction in vascular smooth muscle cells and C6 glioma cells, as well as proliferation and migration. In vivo, the administration of soluble RAGE or genetic deletion of RAGE mitigated LPA-stimulated vascular Akt signaling, autotaxin/LPA-driven phosphorylation of Akt and cyclin D1 in the mammary tissue of transgenic mice vulnerable to carcinogenesis, and ovarian tumor implantation and development. These findings identify novel roles for RAGE as a conduit for LPA signaling and suggest targeting LPA–RAGE interaction as a therapeutic strategy to modify the pathological actions of LPA. The Rockefeller University Press 2012-12-17 /pmc/articles/PMC3526353/ /pubmed/23209312 http://dx.doi.org/10.1084/jem.20120873 Text en © 2012 Rai et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Brief Definitive Report Rai, Vivek Touré, Fatouma Chitayat, Seth Pei, Renjun Song, Fei Li, Qing Zhang, Jinghua Rosario, Rosa Ramasamy, Ravichandran Chazin, Walter J. Schmidt, Ann Marie Lysophosphatidic acid targets vascular and oncogenic pathways via RAGE signaling |
title | Lysophosphatidic acid targets vascular and oncogenic pathways via RAGE signaling |
title_full | Lysophosphatidic acid targets vascular and oncogenic pathways via RAGE signaling |
title_fullStr | Lysophosphatidic acid targets vascular and oncogenic pathways via RAGE signaling |
title_full_unstemmed | Lysophosphatidic acid targets vascular and oncogenic pathways via RAGE signaling |
title_short | Lysophosphatidic acid targets vascular and oncogenic pathways via RAGE signaling |
title_sort | lysophosphatidic acid targets vascular and oncogenic pathways via rage signaling |
topic | Brief Definitive Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3526353/ https://www.ncbi.nlm.nih.gov/pubmed/23209312 http://dx.doi.org/10.1084/jem.20120873 |
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