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

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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Publication Details

Journal
Nature Communications
Published
2024-09-12
DOI
https://doi.org/10.1038/s41467-024-52068-0
Citations
12
Primary Topic
Cardiac Fibrosis and Remodeling
Type
article
Field-Weighted Citation Impact
4.82

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article

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

Atsushi Enomoto, Mikito Takefuji, Yoshimitsu Yura, Toyoaki Murohara et al.
12 citations
Nature Communications
Cardiac Fibrosis and Remodeling
4.82
article

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

Atsushi Enomoto, Mikito Takefuji, Yoshimitsu Yura, Toyoaki Murohara, Nina Wettschureck, Noriyuki Ouchi, Tomoki Hattori, Katsuhiro Kato, Tatsuya Yoshida, Koji Ohashi, Takahiro Okumura, Haruya Kawase, Kohei Inukai, Stefan Offermanns, Satoya Yoshida
article en
12 citations

Abstract

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.

Nature CommunicationsVol. 15(1)
Nagoya University Hospital (JP), Max Planck Institute for Heart and Lung Research (DE), Nagoya University (JP)
Hori Sciences and Arts Foundation, Japan Science Society, Japan Society for the Promotion of Science
Good health and well-being
Openalex Percentile: Top 4%
Cardiac Fibrosis and Remodeling
4.82
DOIOpen Access PDFOpenAlex
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