The proton-sensing G protein-coupled receptor T-cell death-associated gene 8 (TDAG8) shows cardioprotective effects against myocardial infarction

Abstract Myocardial infarction (MI) is an ischaemic heart condition caused by the occlusion of coronary arteries. Following MI, lactic acid from anaerobic glycolysis increases and infiltrating immune cells produce severe inflammation, which leads to acidosis in the ischaemic heart. However, the phys...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Akiomi Nagasaka, Chihiro Mogi, Hiroki Ono, Toshihide Nishi, Yuma Horii, Yuki Ohba, Koichi Sato, Michio Nakaya, Fumikazu Okajima, Hitoshi Kurose
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/79bdd7ecb0b44afb8eab5d5cabbfc604
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:79bdd7ecb0b44afb8eab5d5cabbfc604
record_format	dspace
spelling	oai:doaj.org-article:79bdd7ecb0b44afb8eab5d5cabbfc6042021-12-02T15:05:22ZThe proton-sensing G protein-coupled receptor T-cell death-associated gene 8 (TDAG8) shows cardioprotective effects against myocardial infarction10.1038/s41598-017-07573-22045-2322https://doaj.org/article/79bdd7ecb0b44afb8eab5d5cabbfc6042017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-07573-2https://doaj.org/toc/2045-2322Abstract Myocardial infarction (MI) is an ischaemic heart condition caused by the occlusion of coronary arteries. Following MI, lactic acid from anaerobic glycolysis increases and infiltrating immune cells produce severe inflammation, which leads to acidosis in the ischaemic heart. However, the physiological implication of this pH reduction remains largely unknown. T-cell death-associated gene 8 (TDAG8) is a proton-sensing G protein-coupled receptor found on cardiac macrophages that recognise increases in extracellular protons. We demonstrated that TDAG8 negatively regulates the transcription of the chemokine Ccl20. The infarcted hearts of TDAG8 KO mice showed an increase in CCL20 expression and the number of infiltrating IL-17A-producing γδT cells that express CCR6, a receptor for CCL20. Accordingly, excessive IL-17A production, which is linked to the functional deterioration after MI, was observed in MI-operated TDAG8 KO mice. The survival rate and cardiac function significantly decreased in TDAG8 KO mice compared with those in wild-type mice after MI. Thus, our results suggest that TDAG8 is a key regulator of MI and a potential therapeutic target.Akiomi NagasakaChihiro MogiHiroki OnoToshihide NishiYuma HoriiYuki OhbaKoichi SatoMichio NakayaFumikazu OkajimaHitoshi KuroseNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Akiomi Nagasaka Chihiro Mogi Hiroki Ono Toshihide Nishi Yuma Horii Yuki Ohba Koichi Sato Michio Nakaya Fumikazu Okajima Hitoshi Kurose The proton-sensing G protein-coupled receptor T-cell death-associated gene 8 (TDAG8) shows cardioprotective effects against myocardial infarction
description	Abstract Myocardial infarction (MI) is an ischaemic heart condition caused by the occlusion of coronary arteries. Following MI, lactic acid from anaerobic glycolysis increases and infiltrating immune cells produce severe inflammation, which leads to acidosis in the ischaemic heart. However, the physiological implication of this pH reduction remains largely unknown. T-cell death-associated gene 8 (TDAG8) is a proton-sensing G protein-coupled receptor found on cardiac macrophages that recognise increases in extracellular protons. We demonstrated that TDAG8 negatively regulates the transcription of the chemokine Ccl20. The infarcted hearts of TDAG8 KO mice showed an increase in CCL20 expression and the number of infiltrating IL-17A-producing γδT cells that express CCR6, a receptor for CCL20. Accordingly, excessive IL-17A production, which is linked to the functional deterioration after MI, was observed in MI-operated TDAG8 KO mice. The survival rate and cardiac function significantly decreased in TDAG8 KO mice compared with those in wild-type mice after MI. Thus, our results suggest that TDAG8 is a key regulator of MI and a potential therapeutic target.
format	article
author	Akiomi Nagasaka Chihiro Mogi Hiroki Ono Toshihide Nishi Yuma Horii Yuki Ohba Koichi Sato Michio Nakaya Fumikazu Okajima Hitoshi Kurose
author_facet	Akiomi Nagasaka Chihiro Mogi Hiroki Ono Toshihide Nishi Yuma Horii Yuki Ohba Koichi Sato Michio Nakaya Fumikazu Okajima Hitoshi Kurose
author_sort	Akiomi Nagasaka
title	The proton-sensing G protein-coupled receptor T-cell death-associated gene 8 (TDAG8) shows cardioprotective effects against myocardial infarction
title_short	The proton-sensing G protein-coupled receptor T-cell death-associated gene 8 (TDAG8) shows cardioprotective effects against myocardial infarction
title_full	The proton-sensing G protein-coupled receptor T-cell death-associated gene 8 (TDAG8) shows cardioprotective effects against myocardial infarction
title_fullStr	The proton-sensing G protein-coupled receptor T-cell death-associated gene 8 (TDAG8) shows cardioprotective effects against myocardial infarction
title_full_unstemmed	The proton-sensing G protein-coupled receptor T-cell death-associated gene 8 (TDAG8) shows cardioprotective effects against myocardial infarction
title_sort	proton-sensing g protein-coupled receptor t-cell death-associated gene 8 (tdag8) shows cardioprotective effects against myocardial infarction
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/79bdd7ecb0b44afb8eab5d5cabbfc604
work_keys_str_mv	AT akiominagasaka theprotonsensinggproteincoupledreceptortcelldeathassociatedgene8tdag8showscardioprotectiveeffectsagainstmyocardialinfarction AT chihiromogi theprotonsensinggproteincoupledreceptortcelldeathassociatedgene8tdag8showscardioprotectiveeffectsagainstmyocardialinfarction AT hirokiono theprotonsensinggproteincoupledreceptortcelldeathassociatedgene8tdag8showscardioprotectiveeffectsagainstmyocardialinfarction AT toshihidenishi theprotonsensinggproteincoupledreceptortcelldeathassociatedgene8tdag8showscardioprotectiveeffectsagainstmyocardialinfarction AT yumahorii theprotonsensinggproteincoupledreceptortcelldeathassociatedgene8tdag8showscardioprotectiveeffectsagainstmyocardialinfarction AT yukiohba theprotonsensinggproteincoupledreceptortcelldeathassociatedgene8tdag8showscardioprotectiveeffectsagainstmyocardialinfarction AT koichisato theprotonsensinggproteincoupledreceptortcelldeathassociatedgene8tdag8showscardioprotectiveeffectsagainstmyocardialinfarction AT michionakaya theprotonsensinggproteincoupledreceptortcelldeathassociatedgene8tdag8showscardioprotectiveeffectsagainstmyocardialinfarction AT fumikazuokajima theprotonsensinggproteincoupledreceptortcelldeathassociatedgene8tdag8showscardioprotectiveeffectsagainstmyocardialinfarction AT hitoshikurose theprotonsensinggproteincoupledreceptortcelldeathassociatedgene8tdag8showscardioprotectiveeffectsagainstmyocardialinfarction AT akiominagasaka protonsensinggproteincoupledreceptortcelldeathassociatedgene8tdag8showscardioprotectiveeffectsagainstmyocardialinfarction AT chihiromogi protonsensinggproteincoupledreceptortcelldeathassociatedgene8tdag8showscardioprotectiveeffectsagainstmyocardialinfarction AT hirokiono protonsensinggproteincoupledreceptortcelldeathassociatedgene8tdag8showscardioprotectiveeffectsagainstmyocardialinfarction AT toshihidenishi protonsensinggproteincoupledreceptortcelldeathassociatedgene8tdag8showscardioprotectiveeffectsagainstmyocardialinfarction AT yumahorii protonsensinggproteincoupledreceptortcelldeathassociatedgene8tdag8showscardioprotectiveeffectsagainstmyocardialinfarction AT yukiohba protonsensinggproteincoupledreceptortcelldeathassociatedgene8tdag8showscardioprotectiveeffectsagainstmyocardialinfarction AT koichisato protonsensinggproteincoupledreceptortcelldeathassociatedgene8tdag8showscardioprotectiveeffectsagainstmyocardialinfarction AT michionakaya protonsensinggproteincoupledreceptortcelldeathassociatedgene8tdag8showscardioprotectiveeffectsagainstmyocardialinfarction AT fumikazuokajima protonsensinggproteincoupledreceptortcelldeathassociatedgene8tdag8showscardioprotectiveeffectsagainstmyocardialinfarction AT hitoshikurose protonsensinggproteincoupledreceptortcelldeathassociatedgene8tdag8showscardioprotectiveeffectsagainstmyocardialinfarction
_version_	1718388840630059008

The proton-sensing G protein-coupled receptor T-cell death-associated gene 8 (TDAG8) shows cardioprotective effects against myocardial infarction

Ejemplares similares