空军军医大学学报2026，Vol.47Issue(3)：399-407,9.DOI:10.13276/j.issn.2097-1656.2026.03.014
短期高糖通过渗透压力激活Piezo1影响BV2细胞的极化
Short-term high glucose mediates BV2 microglial polarization via Piezo1 activation by osmotic pressure
摘要
Abstract
Objective To investigate the effect of short-term high glucose stimulation on the polarization of murine microglial cells(BV2)via osmotic pressure changes and its underlying mechanism.Methods High glucose and hyperosmosis cell models were established using glucose(Glu)and mannitol(Mnt),respectively.The effect of short-term extracellular osmotic pressure changes induced by high glucose stimulation on Piezo1 protein expression in BV2 cells was examined by Western blotting.The expression of inflammatory factors and polarization-related proteins in BV2 cells was detected using qRT-PCR,ELISA,and Western blotting.Flow cytometry was used to detect cell surface protein expression and changes in Ca2+influx.Intracellular reactive oxygen species(ROS)levels were measured using a superoxide anion detection kit.The expression of proteins such as NF-κB P65 and HO-1 was further investigated by pharmacologically activating or inhibiting Piezo1 protein function.Results Short-term Glu and iso-osmotic Mnt stimulation significantly upregulated the protein expression of the mechanosensitive ion channel Piezo1 in BV2 microglia(P＜0.05),and induced notable Ca2+influx.DHE detection showed that both Glu and Mnt treatments significantly increased intracellular ROS levels(P＜0.01).This effect was mimicked by the Piezo1-specific agonist Yoda1(P＜0.01)and significantly reversed by the inhibitor GsMTx-4(P＜0.01).Further studies revealed that Glu and Mnt treatments promoted a shift in BV2 cells toward a pro-inflammatory phenotype,characterized by upregulated expression of the surface protein CD86 and the inflammatory factors TNF-α and IL-1β.Western blotting analysis indicated that Glu and Mnt treatments upregulated the expression of mechanotransduction-related proteins(YAP/TAZ,ITGB1)and the key inflammatory pathway protein NF-κB,while downregulating the expression of the antioxidant protein HO-1(P＜0.05).Pharmacological activation of Piezo1 reproduced these protein expression changes,whereas inhibition of Piezo1 produced the opposite effects.Conclusion Short-term high glucose stimulation can activate the Piezo1 channel in BV2 microglial cells via induced osmotic pressure changes,which subsequently mediates Ca2+influx and induces an imbalance between oxidation and antioxidation,leading to a pro-inflammatory phenotypic transformation.关键词
糖尿病神经病变/小胶质细胞/炎症/极化/Piezo1/高糖/氧化应激/钙离子Key words
diabetic neuropathy/microglia/inflammation/polarization/Piezo1/high glucose/oxidative stress/calcium ion分类
医药卫生引用本文复制引用
陈宇豪,沈金澳,陈城明,谢婷珂,刘思达,陈奕玄,汪小兰,樊超,韩静..短期高糖通过渗透压力激活Piezo1影响BV2细胞的极化[J].空军军医大学学报,2026,47(3):399-407,9.基金项目
国家自然科学基金面上项目(82471089) （82471089）
陕西省卫生健康科研创新能力提升计划项目(2025TD-19) （2025TD-19）
西安市科技计划项目(2024JH-YLYB-0324) （2024JH-YLYB-0324）
