Oxidized low‑density lipoprotein upregulates microRNA‑146a via JNK and NF‑κB signaling

  • Authors:
    • Zhenwei Li
    • Shuai Wang
    • Wenting Zhao
    • Zewei Sun
    • Hui Yan
    • Jianhua Zhu
  • View Affiliations

  • Published online on: December 29, 2015     https://doi.org/10.3892/mmr.2015.4729
  • Pages: 1709-1716
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Abstract

Increasing evidence suggested the involvement of microRNA (miR)‑146a in the pathogenesis of multiple diseases, including atherosclerosis, bacterial infection and cancer. However, the mechanism by which miR‑146a is regulated in macrophages exposed to oxidized low‑density lipoprotein (oxLDL) has remained elusive. The present study aimed to explore the molecular pathway of miR‑146a regulation in response to oxLDL. Human THP‑1 macrophages were pre‑treated with small interfering RNA specific for scavenger receptors or with pharmacological inhibitors prior to oxLDL administration. A filter plate screening assay was performed to identify oxLDL‑inducible transcription factors that bind to the miR‑146a promoter. The exact binding sites were mapped by chromatin immunoprecipitation. The effects of miR‑146a on markers of macrophage maturation were studied by flow cytometry. The results revealed that miR‑146a expression was deceased when c‑jun N‑terminal kinase (JNK) or nuclear factor (NF)‑κB signaling was inhibited. By forming a complex with c‑jun, which was promoted by oxLDL, the NF‑κB sub‑unit p65 facilitated the binding of c‑jun to the miR‑146a promoter to trigger transcriptional activation. miR‑146a negatively regulated macrophage maturation by reducing the expression of CD86 and CD80. The present study demonstrated that oxLDL positively regulates miR‑146a via the JNK and NF‑κB pathways in macrophages, and that miR‑146a inhibits inflammatory activation.
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February-2016
Volume 13 Issue 2

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Li Z, Wang S, Zhao W, Sun Z, Yan H and Zhu J: Oxidized low‑density lipoprotein upregulates microRNA‑146a via JNK and NF‑κB signaling. Mol Med Rep 13: 1709-1716, 2016
APA
Li, Z., Wang, S., Zhao, W., Sun, Z., Yan, H., & Zhu, J. (2016). Oxidized low‑density lipoprotein upregulates microRNA‑146a via JNK and NF‑κB signaling. Molecular Medicine Reports, 13, 1709-1716. https://doi.org/10.3892/mmr.2015.4729
MLA
Li, Z., Wang, S., Zhao, W., Sun, Z., Yan, H., Zhu, J."Oxidized low‑density lipoprotein upregulates microRNA‑146a via JNK and NF‑κB signaling". Molecular Medicine Reports 13.2 (2016): 1709-1716.
Chicago
Li, Z., Wang, S., Zhao, W., Sun, Z., Yan, H., Zhu, J."Oxidized low‑density lipoprotein upregulates microRNA‑146a via JNK and NF‑κB signaling". Molecular Medicine Reports 13, no. 2 (2016): 1709-1716. https://doi.org/10.3892/mmr.2015.4729