<scp>GRK5</scp>‐mediated inflammation and fibrosis exert cardioprotective effects during the acute phase of myocardial infarction
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- Akiomi Nagasaka
- Department of Pharmacology and Toxicology, Graduate School of Pharmaceutical Sciences Kyushu University Fukuoka Japan
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- Tsuyoshi Terawaki
- Department of Pharmacology and Toxicology, Graduate School of Pharmaceutical Sciences Kyushu University Fukuoka Japan
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- Makoto Noda
- Department of Pharmacology and Toxicology, Graduate School of Pharmaceutical Sciences Kyushu University Fukuoka Japan
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- Miyuki Takashima
- Department of Pharmacology and Toxicology, Graduate School of Pharmaceutical Sciences Kyushu University Fukuoka Japan
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- Mika Fujino
- Department of Pharmacology and Toxicology, Graduate School of Pharmaceutical Sciences Kyushu University Fukuoka Japan
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- Yuto Yamauchi
- Department of Disease control, Graduate School of Pharmaceutical Sciences Kyushu University Fukuoka Japan
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- Shigeki Arawaka
- Division of Neurology, Department of Internal Medicine IV Osaka Medical College Japan
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- Takeo Kato
- Division of Neurology and Clinical Neuroscience, Department of Internal Medicine III Yamagata University School of Medicine Japan
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- Michio Nakaya
- Department of Pharmacology and Toxicology, Graduate School of Pharmaceutical Sciences Kyushu University Fukuoka Japan
説明
<jats:p>During myocardial infarction (MI), cardiac cells at the infarcted area undergo cell death. In response, cardiac myofibroblasts, which are mainly differentiated from resident fibroblasts upon inflammation, produce extracellular matrix proteins such as collagen to fill the damaged areas of the heart to prevent cardiac rupture. In this study, we identified a cardioprotective role of G‐protein‐coupled receptor kinase 5 (GRK5) in MI. GRK5 expression was found to increase in the mouse heart after MI and was highly expressed in cardiac fibroblasts/myofibroblasts. In fibroblasts/myofibroblasts, GRK5 promoted the expression of inflammation‐related genes through nuclear factor‐κB activation, leading to an increase in the expression levels of fibrosis‐related genes. Bone marrow transfer experiments confirmed that GRK5 in fibroblasts/myofibroblasts, but not in infiltrated macrophages in the infarcted area, is mainly responsible for GRK5‐mediated inflammation in infarcted hearts. In addition, inflammation and fibrosis at the infarcted area were significantly suppressed in GRK5 knockout mice, resulting in increased mortality compared with that in wild‐type mice. These data indicate that GRK5 in cardiac fibroblasts/myofibroblasts promotes inflammation and fibrosis to ameliorate the damage after MI.</jats:p>
収録刊行物
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- FEBS Open Bio
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FEBS Open Bio 13 (2), 380-391, 2023-01-20
Wiley