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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 (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 sign...

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Main Authors: Cao, Yaochen (Author) , Sun, Hongming (Author) , Li, Xitong (Author) , Pommer, Wolfgang (Author) , Xiong, Yingquan (Author) , Chen, Xin (Author) , Chu, Chang (Author) , Yu, Fabiao (Author) , Hocher, Berthold (Author) , Wang, Ziqiang (Author)
Format: Article (Journal)
Language:English
Published: April 2024
In: Cellular signalling
Year: 2024, Volume: 116, Pages: 1-13
ISSN:1873-3913
DOI:10.1016/j.cellsig.2024.111063
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.cellsig.2024.111063
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S0898656824000317
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Author Notes:Yaochen Cao, Hongming Sun, Xitong Li, Wolfgang Pommer, Yingquan Xiong, Xin Chen, Chang Chu, Fabiao Yu, Berthold Hocher, Ziqiang Wang
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Summary: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.
Item Description:Gesehen am 04.02.2025
Online verfügbar: 18. Januar 2024, Artikelversion: 29. Januar 2024
Physical Description:Online Resource
ISSN:1873-3913
DOI:10.1016/j.cellsig.2024.111063

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