1. Academic Validation
  2. TRIM59 expression is regulated by Sp1 and Nrf1 in LPS-activated macrophages through JNK signaling pathway

TRIM59 expression is regulated by Sp1 and Nrf1 in LPS-activated macrophages through JNK signaling pathway

  • Cell Signal. 2020 Mar;67:109522. doi: 10.1016/j.cellsig.2019.109522.
Yanying An 1 Yuqi Ni 1 Zhihao Xu 2 Shuizhen Shi 1 Jiashu He 1 Yu Liu 1 Ke-Yu Deng 1 Mingui Fu 3 Meixiu Jiang 4 Hong-Bo Xin 1
Affiliations

Affiliations

  • 1 The National Engineering Research Center for Bioengineering Drugs and the Technologies, Institute of Translational Medicine, Nanchang University, 999 Xuefu Road, Nanchang, Jiangxi 330031, China.
  • 2 Medical College of Nanchang University, 999 Xuefu Road, Nanchang, Jiangxi 330031, China.
  • 3 Department of Biomedical Science, Shock/Trauma Research Center, School of Medicine, University of Missouri Kansas City, Kansas City, MO 64108, USA.
  • 4 The National Engineering Research Center for Bioengineering Drugs and the Technologies, Institute of Translational Medicine, Nanchang University, 999 Xuefu Road, Nanchang, Jiangxi 330031, China. Electronic address: jiangmxs@163.com.
Abstract

Activated macrophages play an important role in many inflammatory diseases including septic shock and atherosclerosis. TRIM59 has been showed to participate in many pathological processes, such as inflammation, cytotoxicity and tumorigenesis. However, the molecular mechanisms controlling its expression in activated macrophages are not fully understood. Here we report that TRIM59 expression is regulated by Sp1 and Nrf1 in LPS-activated macrophages. TRIM59 is highly expressed in macrophages, and markedly decreased by LPS stimuli in vivo and in vitro. TRIM59 promoter activity is also significantly suppressed by LPS and further analysis demonstrated that Sp1 and Nrf1 directly bound to the proximal promoter of TRIM59 gene. LPS treatment significantly decreased Sp1 expression, nuclear translocation and reduced its binding to the promoter, whereas increased Nrf1 expression, nuclear translocation and enhanced its binding to the promoter. Moreover, LPS-decreased TRIM59 expression was reversed by JNK Inhibitor. Finally, TRIM59 level is significantly decreased during atherosclerosis progression. Taken together, our results demonstrated that TRIM59 expression was precisely regulated by Sp1 and Nrf1 in LPS-activated macrophages, which may be dependent on the activation of JNK signaling pathway and TRIM59 may be a potential therapeutic target for inflammatory diseases such as atherosclerosis.

Keywords

Atherosclerosis; Macrophage; Nrf1; Sp1; TRIM59.

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