GSK343 modulates macrophage M2 polarization through the EZH2/MST1/YAP1 signaling axis to mitigate neurological damage induced by hypercalcemia in CKD mice.

Chronic kidney disease EZH2/MST1/YAP1 axis GSK343 Hypercalcemia Macrophage polarization Neurological injury

Journal

Cellular signalling
ISSN: 1873-3913
Titre abrégé: Cell Signal
Pays: England
ID NLM: 8904683

Informations de publication

Date de publication:
17 Jan 2024
Historique:
received: 16 10 2023
revised: 11 01 2024
accepted: 16 01 2024
medline: 20 1 2024
pubmed: 20 1 2024
entrez: 19 1 2024
Statut: aheadofprint

Résumé

Chronic kidney disease (CKD) often culminates in hypercalcemia, instigating severe neurological injuries that are not yet fully understood. This study unveils a mechanism, where GSK343 ameliorates CKD-induced neural damage in mice by modulating macrophage polarization through the EZH2/MST1/YAP1 signaling axis. Specifically, GSK343 downregulated the expression of histone methyltransferase EZH2 and upregulated MST1, which suppressed YAP1, promoting M2 macrophage polarization and thereby, alleviating neural injury in hypercalcemia arising from renal failure. This molecular pathway introduced herein not only sheds light on the cellular machinations behind CKD-induced neurological harm but also paves the way for potential therapeutic interventions targeting the identified axis, especially considering the M2 macrophage polarization as a potential strategy to mitigate hypercalcemia-induced neural injuries.

Identifiants

DOI: 10.1016/j.cellsig.2024.111063 PMID: 38242267
pubmed: 38242267
pii: S0898-6568(24)00031-7
doi: 10.1016/j.cellsig.2024.111063
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

111063

Informations de copyright

Copyright © 2024. Published by Elsevier Inc.

Déclaration de conflit d'intérêts

Declaration of competing interest The authors declare no competing financial interests.

Auteurs

Yaochen Cao (Y)

Department of Medicine, Hainan Medical University, The First Affiliated Hospital of Hainan Medical University, No. 31 Longhua Road, Haikou 570102, Hannan, China; Department of Nephrology, Charité - Universitätsmedizin Berlin, Campus Mitte, Berlin 10117, Germany; Fifth Department of Medicine (Nephrology/Endocrinology/Rheumatology), University Medical Centre Mannheim, University of Heidelberg, Heidelberg, Germany; Key Laboratory of Emergency and Trauma, Ministry of Education, Key Laboratory of Hainan Trauma and Disaster Rescue, The First Affiliated Hospital of Hainan Medical University, College of Pharmacy, Institute of Functional Materials and Molecular Imaging, College of Emergency and Trauma, Hainan Medical University, Haikou 571199, China.

Hongming Sun (H)

Department of Medicine, Hainan Medical University, The First Affiliated Hospital of Hainan Medical University, No. 31 Longhua Road, Haikou 570102, Hannan, China; Department of Neurology and Neuroscience, Okayama University School of Medicine, Okayama 700-8558, Japan.

Xitong Li (X)

Department of Nephrology, Charité - Universitätsmedizin Berlin, Campus Mitte, Berlin 10117, Germany; Fifth Department of Medicine (Nephrology/Endocrinology/Rheumatology), University Medical Centre Mannheim, University of Heidelberg, Heidelberg, Germany.

Wolfgang Pommer (W)

Kuratorium für Dialyse und Nierentransplantation (KfH) - Bildungszentrum, Martin-Behaim-Str. 20, Neu-Isenburg 63263, Germany.

Yingquan Xiong (Y)

Department of Nephrology, Charité - Universitätsmedizin Berlin, Campus Mitte, Berlin 10117, Germany; Fifth Department of Medicine (Nephrology/Endocrinology/Rheumatology), University Medical Centre Mannheim, University of Heidelberg, Heidelberg, Germany.

Xin Chen (X)

Department of Nephrology, Charité - Universitätsmedizin Berlin, Campus Mitte, Berlin 10117, Germany; Fifth Department of Medicine (Nephrology/Endocrinology/Rheumatology), University Medical Centre Mannheim, University of Heidelberg, Heidelberg, Germany.

Chang Chu (C)

Fifth Department of Medicine (Nephrology/Endocrinology/Rheumatology), University Medical Centre Mannheim, University of Heidelberg, Heidelberg, Germany.

Fabiao Yu (F)

Department of Medicine, Hainan Medical University, The First Affiliated Hospital of Hainan Medical University, No. 31 Longhua Road, Haikou 570102, Hannan, China; Key Laboratory of Emergency and Trauma, Ministry of Education, Key Laboratory of Hainan Trauma and Disaster Rescue, The First Affiliated Hospital of Hainan Medical University, College of Pharmacy, Institute of Functional Materials and Molecular Imaging, College of Emergency and Trauma, Hainan Medical University, Haikou 571199, China. Electronic address: yufabiao@hainmc.edu.cn.

Berthold Hocher (B)

Fifth Department of Medicine (Nephrology/Endocrinology/Rheumatology), University Medical Centre Mannheim, University of Heidelberg, Heidelberg, Germany; Key Laboratory of Emergency and Trauma, Ministry of Education, Key Laboratory of Hainan Trauma and Disaster Rescue, The First Affiliated Hospital of Hainan Medical University, College of Pharmacy, Institute of Functional Materials and Molecular Imaging, College of Emergency and Trauma, Hainan Medical University, Haikou 571199, China; Reproductive and Genetic Hospital of CITIC-Xiangya, Changsha, China; Institute of Medical Diagnostics, IMD Berlin, Berlin, Germany. Electronic address: berthold.hocher@medma.uni-heidelberg.de.

Ziqiang Wang (Z)

Department of Medicine, Hainan Medical University, The First Affiliated Hospital of Hainan Medical University, No. 31 Longhua Road, Haikou 570102, Hannan, China; Key Laboratory of Emergency and Trauma, Ministry of Education, Key Laboratory of Hainan Trauma and Disaster Rescue, The First Affiliated Hospital of Hainan Medical University, College of Pharmacy, Institute of Functional Materials and Molecular Imaging, College of Emergency and Trauma, Hainan Medical University, Haikou 571199, China. Electronic address: ziqiang1986@hainmc.edu.cn.

Classifications MeSH