Protein kinase N promotes cardiac fibrosis in heart failure by fibroblast-to-myofibroblast conversion.
Animals
Heart Failure
/ pathology
Myofibroblasts
/ metabolism
Fibrosis
Fibroblasts
/ metabolism
Mice
Myocardium
/ pathology
Protein Kinase C
/ metabolism
Male
Humans
Disease Models, Animal
Mice, Inbred C57BL
Mice, Knockout
Extracellular Matrix
/ metabolism
Phosphorylation
p38 Mitogen-Activated Protein Kinases
/ metabolism
Signal Transduction
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
12 Sep 2024
12 Sep 2024
Historique:
received:
13
12
2023
accepted:
26
08
2024
medline:
13
9
2024
pubmed:
13
9
2024
entrez:
12
9
2024
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 39266515
doi: 10.1038/s41467-024-52068-0
pii: 10.1038/s41467-024-52068-0
doi:
Substances chimiques
Protein Kinase C
EC 2.7.11.13
protein kinase N
EC 2.7.1.-
p38 Mitogen-Activated Protein Kinases
EC 2.7.11.24
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
7638Subventions
Organisme : Japan Science Society
ID : 23H02903
Informations de copyright
© 2024. The Author(s).
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