Inhibiting the Piezo1 channel protects microglia from acute hyperglycaemia damage through the JNK1 and mTOR signalling pathways

Aim: Diabetes is a high-risk factor for neurocognitive dysfunction. Diabetic acute hyperglycaemia accompanied by high osmotic pressure can induce immune cell dysfunction, but its mechanism of action in brain microglia remains unclear. This study aimed to evaluate the role of the mechanically sensitive ion channel Piezo1 in the dysfunction of microglia in acute hyperglycaemia. Materials and methods: To construct an in vitro acute hyperglycaemia model using the BV2 microglial cell line, Piezo1 in microglia was inhibited by GsMTx4 and siRNA, and the changes in microglial function were further evaluated. Key findings: High concentrations of glucose upregulated the expression of Piezo1, led to weakened cell proliferation and migration, and reduced the immune response to inflammatory stimulating factors (A beta and LPS). Additionally, LPS upregulated Piezo1 in BV2 microglial cultures in vitro. The activation of Piezo1 channels increased the intracellular Ca2+ concentration and reduced the phosphorylation of JNK1 and mTOR. Inhibiting Piezo1 did not affect cell viability at average glucose concentrations but improved acute HCG-induced cell damage and increased the phosphorylation of JNK1 and mTOR, suggesting that the latter modification may be a potential downstream mechanism of Piezo1. Significance: Piezo1 is necessary for microglial damage in acute hyperglycaemia and may become a promising target to treat hyperglycaemic brain injury.

Automated summary

The study reveals that high glucose concentrations upregulate Piezo1 expression, resulting in weakened microglial cell proliferation and migration, as well as reduced immune response to inflammatory stimulating factors. Inhibiting Piezo1 may improve acute hyperglycaemia-induced cell damage, making it a potential target for treating hyperglycaemic brain injury.