Abstract：
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.
摘要：
慢性肾病（CKD）通常以高钙血症告终，煽动尚未完全理解的严重神经损伤。这项研究揭示了一种机制，其中GSK343通过调节巨噬细胞极化通过EZH2/MST1/YAP1信号轴改善小鼠CKD诱导的神经损伤。具体来说,GSK343下调组蛋白甲基转移酶EZH2的表达并上调MST1，从而抑制YAP1，促进M2巨噬细胞极化，从而减轻肾衰竭引起的高钙血症的神经损伤。本文引入的这种分子途径不仅揭示了CKD引起的神经系统损害背后的细胞机制，而且为针对已识别轴的潜在治疗干预铺平了道路。特别是考虑到M2巨噬细胞极化是减轻高钙血症引起的神经损伤的潜在策略。
