2. Academic Validation
  3. Nicotine induces macrophage pyroptosis via LINC01272/miR-515/KLF6 axis

Nicotine induces macrophage pyroptosis via LINC01272/miR-515/KLF6 axis

  • Ecotoxicol Environ Saf. 2023 Jul 19;263:115265. doi: 10.1016/j.ecoenv.2023.115265.
Lianjie Hou 1,  Qin He 2,  Yu Wang 1,  Xixi Feng 1,  Yali Mi 1,  Shuang Li 1,  Jie Feng Deng 1,  Guojun Zhao 3
Affiliations

Affiliations

  • 1 The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan City People's Hospital, Qingyuan 511518, Guangdong, China.
  • 2 Dali University, No. 2 Hongsheng Road, Dali, Yunnan 671003, China.
  • 3 The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan City People's Hospital, Qingyuan 511518, Guangdong, China. Electronic address: zhaoguojun@gzhmu.edu.cn.
PMID: 37478567 DOI: 10.1016/j.ecoenv.2023.115265
Abstract

Nicotine contributes to the causation of atherosclerosis, which the prominent cellular components are macrophages. Long non-coding RNAs (lncRNAs) play an important role in regulating cell functions such as cell proliferation, differentiation and programmed death. However, the function and mechanism of lncRNAs in nicotine-induced macrophage Pyroptosis has not been reported. We screened the deferentially expressed lncRNAs of human carotid artery plaque (GSE97210) and verified them in nicotine-induced Pyroptosis of macrophages. Results showed only LINC01272 was up-regulated in a dose-dependent manner in macrophages. The immunofluorescence staining result confirmed that interfering LINC01272 inhibited nicotine-induced macrophage Pyroptosis. Through bioinformatics analysis, dual luciferase reporter gene assay and qPCR, we identified miR-515 was significantly negatively correlated with the expression of LINC01272, and KLF6 is the target gene of miR-515. Furthermore, our results demonstrated that LINC01272/miR-515/KLF6 axis meditated nicotine-induced macrophage Pyroptosis. In addition, in human peripheral blood mononuclear cells of smoking populations, the expression of GSDMD-N, NLRP3, LINC01272 and KLF6 was significantly increased, while the level of miR-515 was reduced. This study confirmed that nicotine increases the expression of LINC01272 to competitively bind with miR-515 in macrophages, reducing the inhibitory effect of miR-515 on its target gene KLF6, which ultimately induces macrophage Pyroptosis.

Keywords

Macrophages; Nicotine; Non-coding RNA; Pyroptosis; Tobacco smoking.

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