Protein kinase N promotes cardiac fibrosis in heart failure by fibroblast-to-myofibroblast conversion.

Autor: Yoshida S; Department of Cardiology, Nagoya University School of Medicine, Nagoya, Japan., Yoshida T; Department of Cardiology, Nagoya University School of Medicine, Nagoya, Japan., Inukai K; Department of Cardiology, Nagoya University School of Medicine, Nagoya, Japan., Kato K; Department of Cardiology, Nagoya University School of Medicine, Nagoya, Japan., Yura Y; Department of Cardiology, Nagoya University School of Medicine, Nagoya, Japan., Hattori T; Department of Cardiology, Nagoya University School of Medicine, Nagoya, Japan., Enomoto A; Department of Pathology, Nagoya University School of Medicine, Nagoya, Japan., Ohashi K; Department of Molecular Medicine and Cardiology, Nagoya University School of Medicine, Nagoya, Japan., Okumura T; Department of Cardiology, Nagoya University School of Medicine, Nagoya, Japan., Ouchi N; Department of Molecular Medicine and Cardiology, Nagoya University School of Medicine, Nagoya, Japan., Kawase H; Department of Cardiology, Nagoya University School of Medicine, Nagoya, Japan.; Department of Pharmacology, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany., Wettschureck N; Department of Pharmacology, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany., Offermanns S; Department of Pharmacology, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany., Murohara T; Department of Cardiology, Nagoya University School of Medicine, Nagoya, Japan., Takefuji M; Department of Cardiology, Nagoya University School of Medicine, Nagoya, Japan. takefuji@med.nagoya-u.ac.jp.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Sep 12; Vol. 15 (1), pp. 7638. Date of Electronic Publication: 2024 Sep 12.
DOI: 10.1038/s41467-024-52068-0
Abstrakt: 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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