O-GlcNAcylation of NLRP3 Contributes to Lipopolysaccharide-Induced Pyroptosis of Human Gingival Fibroblasts

作者全名："Yang, Hao; Xiao, Li; Wu, Dongxue; Zhang, Tingting; Ge, Ping"

作者地址："[Yang, Hao; Xiao, Li; Wu, Dongxue; Zhang, Tingting] Chongqing Med Univ, Branch Hosp 1, Affilliated Hosp 1, Dept Stomatol, 24 Shiyou Rd, Chongqing 400011, Peoples R China; [Ge, Ping] Chongqing Med Univ, Branch Hosp 1, Affilliated Hosp 1, Dept Internal Med Cardiovasc, 24 Shiyou Rd, Chongqing 400011, Peoples R China"

通信作者："Ge, P (通讯作者)，Chongqing Med Univ, Branch Hosp 1, Affilliated Hosp 1, Dept Internal Med Cardiovasc, 24 Shiyou Rd, Chongqing 400011, Peoples R China."

来源：MOLECULAR BIOTECHNOLOGY

ESI学科分类：BIOLOGY & BIOCHEMISTRY

WOS号：WOS:001047221700001

JCR分区：Q3

影响因子：2.4

年份：2023

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期号：　

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结束页：　

文献类型：Article; Early Access

关键词：Periodontitis; Pyroptosis; Gingival fibroblasts; NLRP3; O-GlcNAcylation

摘要："Periodontitis is a leading chronic oral disorder and poses a serious burden on public health. O-GlcNAc glycosylation (O-GlcNAcylation) is regulated only by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA) and participates in the regulation of human gingival fibroblasts (HGFs) function. Hence, the purpose of this study is to investigate whether HGFs cell function and periodontitis pathogenesis are regulated by O-GlcNAcylation. Herein, we first established cell model of periodontitis induced by lipopolysaccharide (LPS). The cell viability was measured with CCK-8 assay. Pyroptosis was measured by flow cytometry and western blot. The inflammatory factors levels were detected with ELISA kits. Afterward, our findings indicated that LPS elevated the O-GlcNAcylation level of HGFs and inhibition of O-GlcNAcylation improved LPS-induced pyroptosis of HGFs. Mechanistically, LPS heightened the expression of OGT to induce the O-GlcNAcylation of NLRP3. Subsequently, we certified that Thr542 was the O-GlcNAcylation site of NLRP3. More importantly, upregulation of NLRP3 reversed the effects of OGT knockdown on LPS-induced pyroptosis. In general, the current research demonstrated that LPS contributed to the pyroptosis of HGFs by enhancing the OGT expression to promote O-GlcNAcylation of NLRP3, which suggested that O-GlcNAcylation of NLRP3 was a driving factor for periodontitis and offered a novel insight into the treatment of this disease."

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