上睑下垂
基因敲除
免疫印迹
化学
分子生物学
转染
半胱氨酸蛋白酶1
细胞生物学
程序性细胞死亡
基因
细胞凋亡
生物
生物化学
作者
Shouyuan Chi,Suyun Li,Zhiqiang Xu,Gangyi Yang,Yu Song,Zhiwei Liao,Cao Yang,Xinghuo Wu
标识
DOI:10.1016/j.bbrc.2023.02.074
摘要
A study has been conducted to investigate the relationship between DDX3X and nucleus pulposus (NP) pyroptosis. DDX3X and pyroptosis-related proteins (Caspase-1, Full-length GSDMD, Cleaved GSDMD) were measured in compression-induced human NP cells and tissue. DDX3X was overexpressed or knocked down by gene transfection. The expressions of NLRP3, ASC, and pyroptosis-related proteins were detected by Western blot assay. IL-1β and IL-18 were detected by ELISA. HE staining and immunohistochemistry were used to observe the expression of DDX3X, NLRP3, and Caspase-1 in the rat model of compression-induced disc degeneration. DDX3X, NLRP3, and Caspase-1 were highly expressed in degenerated NP tissue. Overexpression of DDX3X induced pyroptosis in NP cells and increased levels of NLRP3, IL-1β, IL-18, and pyroptosis-related proteins. Knockdown of DDX3X showed an opposite trend to overexpression of DDX3X. The NLRP3 inhibitor CY-09 effectively prevented the up-regulation of the expression of IL-1β, IL-18, ASC, Pro-caspase-1, Full-length GSDMD, and Cleaved GSDMD. Increased expression of DDX3X, NLRP3, and Caspase-1 was observed in the rat model of compression-induced disc degeneration. Our study showed that DDX3X mediates pyroptosis of NP cells by upregulating NLRP3 expression, which ultimately leads to intervertebral disc degeneration (IDD). This discovery deepens the understanding of IDD pathogenesis and provides a promising and novel therapeutic target for IDD.
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