The mechanosensitive ion channel Piezo1 modulates the migration and immune response of microglia
Ting Zhu,
Jinghui Guo,
Yong Wu,
Ting Lei,
Jiejun Zhu,
Hui Chen,
Shashwati Kala,
Kin Fung Wong,
Chi Pong Cheung,
Xiaohui Huang,
Xinyi Zhao,
Minyi Yang,
Lei Sun
Affiliations
Ting Zhu
Department of Biomedical Engineering, the Hong Kong Polytechnic University, Hung Hom, Hong Kong SAR 999077, P. R. China
Jinghui Guo
Department of Biomedical Engineering, the Hong Kong Polytechnic University, Hung Hom, Hong Kong SAR 999077, P. R. China
Yong Wu
Department of Biomedical Engineering, the Hong Kong Polytechnic University, Hung Hom, Hong Kong SAR 999077, P. R. China
Ting Lei
Department of Biomedical Engineering, the Hong Kong Polytechnic University, Hung Hom, Hong Kong SAR 999077, P. R. China
Jiejun Zhu
Department of Biomedical Engineering, the Hong Kong Polytechnic University, Hung Hom, Hong Kong SAR 999077, P. R. China
Hui Chen
Biotherapy Centre, the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Cell-gene Therapy Translational Medicine Research Centre, the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
Shashwati Kala
Department of Biomedical Engineering, the Hong Kong Polytechnic University, Hung Hom, Hong Kong SAR 999077, P. R. China
Kin Fung Wong
Department of Biomedical Engineering, the Hong Kong Polytechnic University, Hung Hom, Hong Kong SAR 999077, P. R. China
Chi Pong Cheung
Department of Biomedical Engineering, the Hong Kong Polytechnic University, Hung Hom, Hong Kong SAR 999077, P. R. China
Xiaohui Huang
Department of Biomedical Engineering, the Hong Kong Polytechnic University, Hung Hom, Hong Kong SAR 999077, P. R. China
Xinyi Zhao
Department of Biomedical Engineering, the Hong Kong Polytechnic University, Hung Hom, Hong Kong SAR 999077, P. R. China
Minyi Yang
Department of Biomedical Engineering, the Hong Kong Polytechnic University, Hung Hom, Hong Kong SAR 999077, P. R. China
Lei Sun
Department of Biomedical Engineering, the Hong Kong Polytechnic University, Hung Hom, Hong Kong SAR 999077, P. R. China; Corresponding author
Summary: 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 β-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.
