Jmjd4 Facilitates Pkm2 Degradation in Cardiomyocytes and Is Protective Against Dilated Cardiomyopathy.

Humans Myocytes, Cardiac / metabolism Cardiomyopathy, Dilated / pathology Heart Failure / pathology
HSP70 heat-shock proteins JMJD4 protein, mouse Pkm2 protein cardiomyopathy, dilated chaperone-mediated autophagy hydroxylation mouse

Journal

Circulation
ISSN: 1524-4539
Titre abrégé: Circulation
Pays: United States
ID NLM: 0147763

Informations de publication

Date de publication:
30 05 2023
Historique:
medline: 1 6 2023
pubmed: 18 4 2023
entrez: 17 4 2023
Statut: ppublish

Résumé

A large portion of idiopathic and familial dilated cardiomyopathy (DCM) cases have no obvious causal genetic variant. Although altered response to metabolic stress has been implicated, the molecular mechanisms underlying the pathogenesis of DCM remain elusive. The JMJD family proteins, initially identified as histone deacetylases, have been shown to be involved in many cardiovascular diseases. Despite their increasingly diverse functions, whether JMJD family members play a role in DCM remains unclear. We examined Jmjd4 expression in patients with DCM, and conditionally deleted and overexpressed We found that expression of Jmjd4 is significantly decreased in hearts of patients with DCM. Induced cardiomyocyte-specific deletion of Our results identified a novel role of Jmjd4 in maintaining metabolic homeostasis in adult cardiomyocytes by degrading Pkm2 and suggest that Jmjd4 and Pkm2 may be therapeutically targeted to treat DCM, and other cardiac diseases with metabolic dysfunction, as well.

Sections du résumé

BACKGROUND
A large portion of idiopathic and familial dilated cardiomyopathy (DCM) cases have no obvious causal genetic variant. Although altered response to metabolic stress has been implicated, the molecular mechanisms underlying the pathogenesis of DCM remain elusive. The JMJD family proteins, initially identified as histone deacetylases, have been shown to be involved in many cardiovascular diseases. Despite their increasingly diverse functions, whether JMJD family members play a role in DCM remains unclear.
METHODS
We examined Jmjd4 expression in patients with DCM, and conditionally deleted and overexpressed
RESULTS
We found that expression of Jmjd4 is significantly decreased in hearts of patients with DCM. Induced cardiomyocyte-specific deletion of
CONCLUSIONS
Our results identified a novel role of Jmjd4 in maintaining metabolic homeostasis in adult cardiomyocytes by degrading Pkm2 and suggest that Jmjd4 and Pkm2 may be therapeutically targeted to treat DCM, and other cardiac diseases with metabolic dysfunction, as well.

Identifiants

DOI: 10.1161/CIRCULATIONAHA.123.064121 PMID: 37066795
pubmed: 37066795
doi: 10.1161/CIRCULATIONAHA.123.064121
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1684-1704

Auteurs

Yansong Tang (Y)

Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, China (Y.T., Y.S., T.M., Y.X., D.X.).

Mengying Feng (M)

Institute for Regenerative Medicine, Shanghai East Hospital, Shanghai Institute of Stem Cell Research and Clinical Translation, Shanghai Key Laboratory of Signaling and Disease Research, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, China (M.F., H.Z., S.S., Y.Z., K.W.).

Yang Su (Y)

Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, China (Y.T., Y.S., T.M., Y.X., D.X.).

Teng Ma (T)

Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, China (Y.T., Y.S., T.M., Y.X., D.X.).

Hongjie Zhang (H)

Institute for Regenerative Medicine, Shanghai East Hospital, Shanghai Institute of Stem Cell Research and Clinical Translation, Shanghai Key Laboratory of Signaling and Disease Research, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, China (M.F., H.Z., S.S., Y.Z., K.W.).

Hongchun Wu (H)

Department of Cardiovascular Surgery of the First Affiliated Hospital & Institute for Cardiovascular Science, Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Protection, Medical College, Soochow University, Suzhou, China (H.W., S.H.).

Xiaoyu Wang (X)

Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, China (X.W.).

Shuyue Shi (S)

Institute for Regenerative Medicine, Shanghai East Hospital, Shanghai Institute of Stem Cell Research and Clinical Translation, Shanghai Key Laboratory of Signaling and Disease Research, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, China (M.F., H.Z., S.S., Y.Z., K.W.).
Department of Cardiovascular Surgery of the First Affiliated Hospital & Institute for Cardiovascular Science, Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Protection, Medical College, Soochow University, Suzhou, China (H.W., S.H.).

Ying Zhang (Y)

Institute for Regenerative Medicine, Shanghai East Hospital, Shanghai Institute of Stem Cell Research and Clinical Translation, Shanghai Key Laboratory of Signaling and Disease Research, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, China (M.F., H.Z., S.S., Y.Z., K.W.).

Yawei Xu (Y)

Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, China (Y.T., Y.S., T.M., Y.X., D.X.).

Shijun Hu (S)

Department of Cardiovascular Surgery of the First Affiliated Hospital & Institute for Cardiovascular Science, Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Protection, Medical College, Soochow University, Suzhou, China (H.W., S.H.).
ORCID: 0000-0002-0068-8429

Ke Wei (K)

Institute for Regenerative Medicine, Shanghai East Hospital, Shanghai Institute of Stem Cell Research and Clinical Translation, Shanghai Key Laboratory of Signaling and Disease Research, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, China (M.F., H.Z., S.S., Y.Z., K.W.).
ORCID: 0000-0001-8542-2146

Dachun Xu (D)

Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, China (Y.T., Y.S., T.M., Y.X., D.X.).
ORCID: 0000-0002-4123-6613

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Jmjd4 Facilitates Pkm2 Degradation in...
questionsmedicales.fr › Cellules › Cellules musculaires › Myocytes cardiaques › Jmjd4 Facilitates Pkm2 Degradation in...
questionsmedicales.fr › Malformations et maladies congénitales, héréditaires et néonatales › Maladies génétiques congénitales › Laminopathies › Cardiomyopathie dilatée › Jmjd4 Facilitates Pkm2 Degradation in...
questionsmedicales.fr › Maladies cardiovasculaires › Cardiopathies › Défaillance cardiaque › Jmjd4 Facilitates Pkm2 Degradation in...