长链非编码RNA-Gm17586通过促进NLRP3与Tnip1结合来抑制鼠伤寒沙门氏菌介导的细胞焦亡。

LncRNA-Gm17586 inhibits S.typhimurium mediated pyroptosis by promoting NLRP3 and Tnip1 binding.

作者信息

An Zhiyuan, Ding Wenyi

机构信息

Medical Research Center, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100020, China.

Department of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, China.

出版信息

Sci Rep. 2025 Feb 25;15(1):6713. doi: 10.1038/s41598-025-91296-2.

DOI:10.1038/s41598-025-91296-2

PMID:40000898

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11861967/

Abstract

The aim of this study is to identify the lncRNA that directly interacts with NLRP3 molecules in RAW264.7 cells infected with S. typhimurium and its role in S. typhimurium-mediated pyroptosis. We have identified LncRNA-Gm17586, which directly interacts with NLRP3 in RAW264.7 cells infected with S. typhimurium. LncRNA-Gm17586 inhibits S. typhimurium-mediated pyroptosis in RAW264.7 cells. Overexpression of LncRNA-Gm17586 not only directly suppresses NLRP3 inflammasome activation but also enhances the binding affinity between Tnip1 and NLRP3, thereby indirectly facilitating Tnip1-mediated inhibition of the NLRP3 inflammasome. Consequently, this dual mechanism effectively inhibits S. typhimurium-induced pyroptosis. Our results demonstrate that LncRNA-Gm17586 directly interacts with NLRP3 during S. typhimurium-mediated pyroptosis and inhibits this process by enhancing the interaction between Tnip1 and NLRP3.

摘要

本研究的目的是鉴定在感染鼠伤寒沙门氏菌的RAW264.7细胞中与NLRP3分子直接相互作用的lncRNA及其在鼠伤寒沙门氏菌介导的细胞焦亡中的作用。我们已经鉴定出LncRNA-Gm17586，它在感染鼠伤寒沙门氏菌的RAW264.7细胞中与NLRP3直接相互作用。LncRNA-Gm17586抑制RAW264.7细胞中鼠伤寒沙门氏菌介导的细胞焦亡。LncRNA-Gm17586的过表达不仅直接抑制NLRP3炎性小体的激活，还增强了Tnip1与NLRP3之间的结合亲和力，从而间接促进Tnip1介导的对NLRP3炎性小体的抑制。因此，这种双重机制有效地抑制了鼠伤寒沙门氏菌诱导的细胞焦亡。我们的结果表明，LncRNA-Gm17586在鼠伤寒沙门氏菌介导的细胞焦亡过程中与NLRP3直接相互作用，并通过增强Tnip1与NLRP3之间的相互作用来抑制这一过程。