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RAGE ligands stimulate angiotensin II type I receptor (AT1) via RAGE/AT1 complex on the cell membrane

The receptor for advanced glycation end-products (RAGE) and the G protein-coupled angiotensin II (AngII) type I receptor (AT1) play a central role in cardiovascular diseases. It was recently reported that RAGE modifies AngII-mediated AT1 activation via the membrane oligomeric complex of the two rece...

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Autores principales: Yokoyama, Serina, Kawai, Tatsuo, Yamamoto, Koichi, Yibin, Huang, Yamamoto, Hiroko, Kakino, Akemi, Takeshita, Hikari, Nozato, Yoichi, Fujimoto, Taku, Hongyo, Kazuhiro, Takahashi, Toshimasa, Nakagami, Futoshi, Akasaka, Hiroshi, Takami, Yoichi, Takeya, Yasushi, Sugimoto, Ken, Sawamura, Tatsuya, Rakugi, Hiromi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7952713/
https://www.ncbi.nlm.nih.gov/pubmed/33707701
http://dx.doi.org/10.1038/s41598-021-85312-4
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author Yokoyama, Serina
Kawai, Tatsuo
Yamamoto, Koichi
Yibin, Huang
Yamamoto, Hiroko
Kakino, Akemi
Takeshita, Hikari
Nozato, Yoichi
Fujimoto, Taku
Hongyo, Kazuhiro
Takahashi, Toshimasa
Nakagami, Futoshi
Akasaka, Hiroshi
Takami, Yoichi
Takeya, Yasushi
Sugimoto, Ken
Sawamura, Tatsuya
Rakugi, Hiromi
author_facet Yokoyama, Serina
Kawai, Tatsuo
Yamamoto, Koichi
Yibin, Huang
Yamamoto, Hiroko
Kakino, Akemi
Takeshita, Hikari
Nozato, Yoichi
Fujimoto, Taku
Hongyo, Kazuhiro
Takahashi, Toshimasa
Nakagami, Futoshi
Akasaka, Hiroshi
Takami, Yoichi
Takeya, Yasushi
Sugimoto, Ken
Sawamura, Tatsuya
Rakugi, Hiromi
author_sort Yokoyama, Serina
collection PubMed
description The receptor for advanced glycation end-products (RAGE) and the G protein-coupled angiotensin II (AngII) type I receptor (AT1) play a central role in cardiovascular diseases. It was recently reported that RAGE modifies AngII-mediated AT1 activation via the membrane oligomeric complex of the two receptors. In this study, we investigated the presence of the different directional crosstalk in this phenomenon, that is, the RAGE/AT1 complex plays a role in the signal transduction pathway of RAGE ligands. We generated Chinese hamster ovary (CHO) cells stably expressing RAGE and AT1, mutated AT1, or AT2 receptor. The activation of two types of G protein α-subunit, Gq and Gi, was estimated through the accumulation of inositol monophosphate and the inhibition of forskolin-induced cAMP production, respectively. Rat kidney epithelial cells were used to assess RAGE ligand-induced cellular responses. We determined that RAGE ligands activated Gi, but not Gq, only in cells expressing RAGE and wildtype AT1. The activation was inhibited by an AT1 blocker (ARB) as well as a RAGE inhibitor. ARBs inhibited RAGE ligand-induced ERK phosphorylation, NF-κB activation, and epithelial–mesenchymal transition of rat renal epithelial cells. Our findings suggest that the activation of AT1 plays a central role in RAGE-mediated cellular responses and elucidate the role of a novel molecular mechanism in the development of cardiovascular diseases.
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spelling pubmed-79527132021-03-15 RAGE ligands stimulate angiotensin II type I receptor (AT1) via RAGE/AT1 complex on the cell membrane Yokoyama, Serina Kawai, Tatsuo Yamamoto, Koichi Yibin, Huang Yamamoto, Hiroko Kakino, Akemi Takeshita, Hikari Nozato, Yoichi Fujimoto, Taku Hongyo, Kazuhiro Takahashi, Toshimasa Nakagami, Futoshi Akasaka, Hiroshi Takami, Yoichi Takeya, Yasushi Sugimoto, Ken Sawamura, Tatsuya Rakugi, Hiromi Sci Rep Article The receptor for advanced glycation end-products (RAGE) and the G protein-coupled angiotensin II (AngII) type I receptor (AT1) play a central role in cardiovascular diseases. It was recently reported that RAGE modifies AngII-mediated AT1 activation via the membrane oligomeric complex of the two receptors. In this study, we investigated the presence of the different directional crosstalk in this phenomenon, that is, the RAGE/AT1 complex plays a role in the signal transduction pathway of RAGE ligands. We generated Chinese hamster ovary (CHO) cells stably expressing RAGE and AT1, mutated AT1, or AT2 receptor. The activation of two types of G protein α-subunit, Gq and Gi, was estimated through the accumulation of inositol monophosphate and the inhibition of forskolin-induced cAMP production, respectively. Rat kidney epithelial cells were used to assess RAGE ligand-induced cellular responses. We determined that RAGE ligands activated Gi, but not Gq, only in cells expressing RAGE and wildtype AT1. The activation was inhibited by an AT1 blocker (ARB) as well as a RAGE inhibitor. ARBs inhibited RAGE ligand-induced ERK phosphorylation, NF-κB activation, and epithelial–mesenchymal transition of rat renal epithelial cells. Our findings suggest that the activation of AT1 plays a central role in RAGE-mediated cellular responses and elucidate the role of a novel molecular mechanism in the development of cardiovascular diseases. Nature Publishing Group UK 2021-03-11 /pmc/articles/PMC7952713/ /pubmed/33707701 http://dx.doi.org/10.1038/s41598-021-85312-4 Text en © The Author(s) 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Yokoyama, Serina
Kawai, Tatsuo
Yamamoto, Koichi
Yibin, Huang
Yamamoto, Hiroko
Kakino, Akemi
Takeshita, Hikari
Nozato, Yoichi
Fujimoto, Taku
Hongyo, Kazuhiro
Takahashi, Toshimasa
Nakagami, Futoshi
Akasaka, Hiroshi
Takami, Yoichi
Takeya, Yasushi
Sugimoto, Ken
Sawamura, Tatsuya
Rakugi, Hiromi
RAGE ligands stimulate angiotensin II type I receptor (AT1) via RAGE/AT1 complex on the cell membrane
title RAGE ligands stimulate angiotensin II type I receptor (AT1) via RAGE/AT1 complex on the cell membrane
title_full RAGE ligands stimulate angiotensin II type I receptor (AT1) via RAGE/AT1 complex on the cell membrane
title_fullStr RAGE ligands stimulate angiotensin II type I receptor (AT1) via RAGE/AT1 complex on the cell membrane
title_full_unstemmed RAGE ligands stimulate angiotensin II type I receptor (AT1) via RAGE/AT1 complex on the cell membrane
title_short RAGE ligands stimulate angiotensin II type I receptor (AT1) via RAGE/AT1 complex on the cell membrane
title_sort rage ligands stimulate angiotensin ii type i receptor (at1) via rage/at1 complex on the cell membrane
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7952713/
https://www.ncbi.nlm.nih.gov/pubmed/33707701
http://dx.doi.org/10.1038/s41598-021-85312-4
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