CXCR7 ameliorates myocardial infarction as a β-arrestin-biased receptor
| Autor: | Hironori Hara, Masahiro Satoh, Yuichi Ikeda, Norihiko Takeda, Satoshi Bujo, Kinya Otsu, Yoshihiro Motozawa, Hidetoshi Kumagai, Issei Komuro, Toshiyuki Ko, Mutsuo Harada, Haruhiro Toko, Haruka Yanagisawa-Murakami, Norifumi Takeda, Shintaro Yamada, Tatsuyuki Sato, Takayuki Fujiwara, Hiroyuki Morita, Seitaro Nomura, Masato Ishizuka, Jiaxi Guo |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
MAPK/ERK pathway Agonist medicine.medical_specialty Cell biology medicine.drug_class Molecular biology Science Cardiology 030204 cardiovascular system & hematology Article 03 medical and health sciences Chemokine receptor 0302 clinical medicine Internal medicine medicine Arrestin Extracellular Myocardial infarction Receptor Multidisciplinary Kinase business.industry medicine.disease 030104 developmental biology Endocrinology Medicine business |
| Zdroj: | Scientific Reports Scientific Reports, Vol 11, Iss 1, Pp 1-12 (2021) |
| ISSN: | 2045-2322 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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