GSK343 通过 EZH2/MST1/YAP1 信号轴调节巨噬细胞 M2 极化，减轻 CKD 小鼠高钙血症引起的神经损伤。
GSK343 modulates macrophage M2 polarization through the EZH2/MST1/YAP1 signaling axis to mitigate neurological damage induced by hypercalcemia in CKD mice.
机构信息
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.
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.
出版信息
Cell Signal. 2024 Apr;116:111063. doi: 10.1016/j.cellsig.2024.111063. Epub 2024 Jan 18.
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.
慢性肾脏病（CKD）常导致高钙血症，引发严重的神经损伤，但其具体机制尚不完全清楚。本研究揭示了一种机制，即 GSK343 通过 EZH2/MST1/YAP1 信号轴调节巨噬细胞极化，从而改善 CKD 诱导的小鼠神经损伤。具体来说，GSK343 下调组蛋白甲基转移酶 EZH2 的表达，上调 MST1，抑制 YAP1，促进 M2 型巨噬细胞极化，从而减轻肾衰竭引起的高钙血症导致的神经损伤。本研究中提出的分子途径不仅阐明了 CKD 诱导的神经损伤背后的细胞机制，还为针对所确定轴的潜在治疗干预措施铺平了道路，特别是考虑到 M2 型巨噬细胞极化作为减轻高钙血症诱导的神经损伤的一种潜在策略。
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