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Publication : The mechanosensitive ion channel Piezo1 modulates the migration and immune response of microglia.

First Author  Zhu T Year  2023
Journal  iScience Volume  26
Issue  2 Pages  105993
PubMed ID  36798430 Mgi Jnum  J:347454
Mgi Id  MGI:7437064 Doi  10.1016/j.isci.2023.105993
Citation  Zhu T, et al. (2023) The mechanosensitive ion channel Piezo1 modulates the migration and immune response of microglia. iScience 26(2):105993
abstractText  Microglia are the brain's resident immune cells, performing surveillance to promote homeostasis and healthy functioning. While microglial chemical signaling is well-studied, mechanical cues regulating their function are less well-understood. Here, we investigate the role of the mechanosensitive ion channel Piezo1 in microglia migration, pro-inflammatory cytokine production, and stiffness sensing. In Piezo1 knockout transgenic mice, we demonstrated the functional expression of Piezo1 in microglia and identified genes whose expression was consequently affected. Functional assays revealed that Piezo1 deficiency in microglia enhanced migration toward amyloid beta-protein, and decreased levels of pro-inflammatory cytokines produced upon stimulation by lipopolysaccharide, both in vitro and in vivo. The phenomenon could be mimicked or reversed chemically using a Piezo1-specific agonist or antagonist. Finally, we also showed that Piezo1 mediated the effect of substrate stiffness-induced migration and cytokine expression. Altogether, we show that Piezo1 is an important molecular mediator for microglia, its activation modulating microglial migration and immune responses.
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