Piezo1 activates the NLRP3 inflammasome in nucleus pulposus cell-mediated by Ca2+/NF-κB pathway
Piezo1 activates the NLRP3 inflammasome in nucleus pulposus cell-mediated by Ca2+/NF-κB pathway
复制标题
Piezo1 通过 Ca2/NF-kappa B 通路介导激活髓核细胞中的 NLRP3 炎症小体
DOI：
10.1016/j.intimp.2020.106681
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发表时间：
2020-08-01
影响因子：
5.6
通讯作者：
Zhang, Haining
中科院分区：
文献类型：
--
作者：
Sun, Yi;Leng, Ping;Zhang, Haining
Studying and understanding the mechanism of inflammation in nucleus pulposus is the key to understand and prevent intervertebral disc degeneration. We propose a model of mechanical sensitive ion channel Piezo1 mediated inflammation of nucleus pulposus cells. Piezo1 can up-regulate the level of interleukin-1 beta (IL-1 beta) in nucleus pulposus cells once it is activated. It is suggested that Piezo1 may mediate inflammation by activating Nod-like receptor protein 3 (NLRP3) inflammasome to accelerate the production and maturation of IL-1 beta. The primary objective of this study was to explore whether Piezo1 activates NLRP3 inflammasome in nucleus pulposus cells. Piezo1 sensitization was induced by mechanical stretch following which we analyzed the priming and assembly of NLRP3 inflammasome and also studied if the downstream Ca2+/NF-kappa B pathway mediated this activation in nucleus pulposus cells. The expression of Piezo1 and NLRP3 inflammasome increased in a timedependent manner upon mechanical stretch. Piezo1 activation promoted NLRP3 inflammasome assembly, which was demonstrated by the upregulation of caspase-1 activation and IL-1 beta production. Transfection of Piezo1-siRNA reversed this process. The inhibition of Ca2+/NF-kappa B pathway reduced Piezo1-dependent activation of NLRP3 inflammasome. Thus, we propose that activation of NLRP3 inflammasome in nucleus pulposus cells mediated by Piezo1 through the Ca2+/NF-kappa B pathway is a novel pathogenesis for the progress of intervertebral disc degeneration. As per our knowledge this is the first study which has provided evidence linking Piezo1-mediated inflammation in nucleus pulposus cells with the production of NLRP3 inflammasome.
