CXCR7 ameliorates myocardial infarction as a β-arrestin-biased receptor
Abstract Most seven transmembrane receptors (7TMRs) are G protein-coupled receptors; however, some 7TMRs evoke intracellular signals through β-arrestin as a biased receptor. As several β-arrestin-biased agonists have been reported to be cardioprotective, we examined the role of the chemokine recepto...
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Nature Portfolio
2021
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oai:doaj.org-article:063313f872cf4f639b03da0520f970112021-12-02T13:30:22ZCXCR7 ameliorates myocardial infarction as a β-arrestin-biased receptor10.1038/s41598-021-83022-52045-2322https://doaj.org/article/063313f872cf4f639b03da0520f970112021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-83022-5https://doaj.org/toc/2045-2322Abstract Most seven transmembrane receptors (7TMRs) are G protein-coupled receptors; however, some 7TMRs evoke intracellular signals through β-arrestin as a biased receptor. As several β-arrestin-biased agonists have been reported to be cardioprotective, we examined the role of the chemokine receptor CXCR7 as a β-arrestin-biased receptor in the heart. Among 510 7TMR genes examined, Cxcr7 was the most abundantly expressed in the murine heart. Single-cell RNA-sequencing analysis revealed that Cxcr7 was abundantly expressed in cardiomyocytes and fibroblasts. Cardiomyocyte-specific Cxcr7 null mice showed more prominent cardiac dilatation and dysfunction than control mice 4 weeks after myocardial infarction. In contrast, there was no difference in cardiac phenotypes between fibroblast-specific Cxcr7-knockout mice and control mice even after myocardial infarction. TC14012, a specific agonist of CXCR7, significantly recruited β-arrestin to CXCR7 in CXCR7-expressing cells and activated extracellular signal-regulated kinase (ERK) in neonatal rat cardiomyocytes. Cxcr7 expression was significantly increased and ERK was activated in the border zone of the heart in control, but not Cxcr7 null mice. These results indicate that the abundantly expressed CXCR7 in cardiomyocytes may play a protective role in the heart as a β-arrestin-biased receptor and that CXCR7 may be a novel therapeutic target for myocardial infarction.Masato IshizukaMutsuo HaradaSeitaro NomuraToshiyuki KoYuichi IkedaJiaxi GuoSatoshi BujoHaruka Yanagisawa-MurakamiMasahiro SatohShintaro YamadaHidetoshi KumagaiYoshihiro MotozawaHironori HaraTakayuki FujiwaraTatsuyuki SatoNorifumi TakedaNorihiko TakedaKinya OtsuHiroyuki MoritaHaruhiro TokoIssei KomuroNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021) |
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DOAJ |
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Medicine R Science Q Masato Ishizuka Mutsuo Harada Seitaro Nomura Toshiyuki Ko Yuichi Ikeda Jiaxi Guo Satoshi Bujo Haruka Yanagisawa-Murakami Masahiro Satoh Shintaro Yamada Hidetoshi Kumagai Yoshihiro Motozawa Hironori Hara Takayuki Fujiwara Tatsuyuki Sato Norifumi Takeda Norihiko Takeda Kinya Otsu Hiroyuki Morita Haruhiro Toko Issei Komuro CXCR7 ameliorates myocardial infarction as a β-arrestin-biased receptor |
| description |
Abstract Most seven transmembrane receptors (7TMRs) are G protein-coupled receptors; however, some 7TMRs evoke intracellular signals through β-arrestin as a biased receptor. As several β-arrestin-biased agonists have been reported to be cardioprotective, we examined the role of the chemokine receptor CXCR7 as a β-arrestin-biased receptor in the heart. Among 510 7TMR genes examined, Cxcr7 was the most abundantly expressed in the murine heart. Single-cell RNA-sequencing analysis revealed that Cxcr7 was abundantly expressed in cardiomyocytes and fibroblasts. Cardiomyocyte-specific Cxcr7 null mice showed more prominent cardiac dilatation and dysfunction than control mice 4 weeks after myocardial infarction. In contrast, there was no difference in cardiac phenotypes between fibroblast-specific Cxcr7-knockout mice and control mice even after myocardial infarction. TC14012, a specific agonist of CXCR7, significantly recruited β-arrestin to CXCR7 in CXCR7-expressing cells and activated extracellular signal-regulated kinase (ERK) in neonatal rat cardiomyocytes. Cxcr7 expression was significantly increased and ERK was activated in the border zone of the heart in control, but not Cxcr7 null mice. These results indicate that the abundantly expressed CXCR7 in cardiomyocytes may play a protective role in the heart as a β-arrestin-biased receptor and that CXCR7 may be a novel therapeutic target for myocardial infarction. |
| format |
article |
| author |
Masato Ishizuka Mutsuo Harada Seitaro Nomura Toshiyuki Ko Yuichi Ikeda Jiaxi Guo Satoshi Bujo Haruka Yanagisawa-Murakami Masahiro Satoh Shintaro Yamada Hidetoshi Kumagai Yoshihiro Motozawa Hironori Hara Takayuki Fujiwara Tatsuyuki Sato Norifumi Takeda Norihiko Takeda Kinya Otsu Hiroyuki Morita Haruhiro Toko Issei Komuro |
| author_facet |
Masato Ishizuka Mutsuo Harada Seitaro Nomura Toshiyuki Ko Yuichi Ikeda Jiaxi Guo Satoshi Bujo Haruka Yanagisawa-Murakami Masahiro Satoh Shintaro Yamada Hidetoshi Kumagai Yoshihiro Motozawa Hironori Hara Takayuki Fujiwara Tatsuyuki Sato Norifumi Takeda Norihiko Takeda Kinya Otsu Hiroyuki Morita Haruhiro Toko Issei Komuro |
| author_sort |
Masato Ishizuka |
| title |
CXCR7 ameliorates myocardial infarction as a β-arrestin-biased receptor |
| title_short |
CXCR7 ameliorates myocardial infarction as a β-arrestin-biased receptor |
| title_full |
CXCR7 ameliorates myocardial infarction as a β-arrestin-biased receptor |
| title_fullStr |
CXCR7 ameliorates myocardial infarction as a β-arrestin-biased receptor |
| title_full_unstemmed |
CXCR7 ameliorates myocardial infarction as a β-arrestin-biased receptor |
| title_sort |
cxcr7 ameliorates myocardial infarction as a β-arrestin-biased receptor |
| publisher |
Nature Portfolio |
| publishDate |
2021 |
| url |
https://doaj.org/article/063313f872cf4f639b03da0520f97011 |
| work_keys_str_mv |
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1718392894334697472 |