心力衰竭
肌成纤维细胞
成纤维细胞
纤维化
心脏纤维化
细胞外基质
医学
射血分数
心肌纤维化
内科学
磷酸化
蛋白激酶A
细胞生物学
心脏病学
癌症研究
生物
细胞培养
遗传学
作者
Shigekata Yoshida,Tatsuya Yoshida,Kohei Inukai,Katsuhiro Kato,Yoshimitsu Yura,Tomoki Hattori,Atsushi Enomoto,Koji Ohashi,Takahiro Okumura,Noriyuki Ouchi,Hirokazu Kawase,Nina Wettschureck,Stefan Offermanns,Toyoaki Murohara,Mikito Takefuji
标识
DOI:10.1038/s41467-024-52068-0
摘要
Chronic fibrotic tissue disrupts various organ functions. Despite significant advances in therapies, mortality and morbidity due to heart failure remain high, resulting in poor quality of life. Beyond the cardiomyocyte-centric view of heart failure, it is now accepted that alterations in the interstitial extracellular matrix (ECM) also play a major role in the development of heart failure. Here, we show that protein kinase N (PKN) is expressed in cardiac fibroblasts. Furthermore, PKN mediates the conversion of fibroblasts into myofibroblasts, which plays a central role in secreting large amounts of ECM proteins via p38 phosphorylation signaling. Fibroblast-specific deletion of PKN led to a reduction of myocardial fibrotic changes and cardiac dysfunction in mice models of ischemia-reperfusion or heart failure with preserved ejection fraction. Our results indicate that PKN is a therapeutic target for cardiac fibrosis in heart failure.
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