Circular RNA hsa_circ_0008726 Targets the hsa-miR-206-3p/KLF4 Axis to Modulate 4,4'-Methylene Diphenyl Diisocyanate-Glutathione Conjugate-Induced Chemokine Transcription in Macrophages.

IF 5.1 2区 生物学 Q2 CELL BIOLOGY
Cells Pub Date : 2024-10-18 DOI:10.3390/cells13201725
Chen-Chung Lin, Brandon F Law, Justin M Hettick
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引用次数: 0

Abstract

Exposure to 4,4'-methylene diphenyl diisocyanate (MDI) in the workplace may lead to the development of occupational asthma (OA). However, the specific mechanism(s) by which MDI induces OA are poorly understood. Previous reports have demonstrated that MDI and MDI-glutathione (GSH) conjugate exposure downregulates endogenous human/murine (hsa/mmu)-microRNA(miR)-206-3p, resulting in the activation of mmu/hsa-miR-206-3p-regulated signaling pathways in macrophages. Circular RNAs (circRNAs) regulate many important biological processes by targeting endogenous miRs; however, whether MDI/MDI-GSH exposure may influence circRNA expressions is unknown. Several circRNAs have been identified that regulate hsa-miR-206-3p. We hypothesize that MDI-GSH conjugate exposure induces endogenous circRNA(s) to regulate hsa-miR-206-3p in macrophages. The expression of candidate hsa-miR-206-3p-binding circRNAs was determined from MDI-GSH conjugate-treated differentiated THP-1 macrophages using RT-qPCR. MDI-GSH exposures induced hsa_circ_0008726 and its host gene transcript DNAJB6, whereas other circRNA(s) examined were either not detected or unchanged. RNA-induced silencing complex-immunoprecipitation (RISC-IP) experiments confirm that hsa-miR-206-3p can bind to hsa_circ_0008726. The expressions of endogenous hsa-miR-206-3p, hsa-miR-206-3p-regulated KLF4, and KLF4-activated M2 macrophage-associated markers and chemokines were up-/down-regulated by transfection of hsa_circ_0008726 siRNAs or hsa_circ_0008726 overexpression plasmid in macrophages, respectively. These results suggest MDI-GSH exposure downregulates hsa-miR-206-3p via induction of endogenous hsa_circ_0008726/DNAJB6, resulting in the upregulation of hsa-miR-206-3p-mediated regulations in macrophages.

环状 RNA hsa_circ_0008726 靶向 hsa-miR-206-3p/KLF4 轴,调节巨噬细胞中 4,4'-亚甲基二苯基二异氰酸酯-谷胱甘肽共轭物诱导的趋化因子转录。
在工作场所接触 4,4'-亚甲基二苯基二异氰酸酯(MDI)可能会导致职业性哮喘(OA)的发生。然而,人们对 MDI 诱发职业性哮喘的具体机制知之甚少。以前的报告表明,接触 MDI 和 MDI-谷胱甘肽(GSH)共轭物会下调内源性人/鼠(hsa/mmu)-microRNA(miR)-206-3p,从而激活巨噬细胞中 mmu/hsa-miR-206-3p 调节的信号通路。循环 RNA(circRNA)通过靶向内源性 miR 来调节许多重要的生物过程;然而,MDI/MDI-GSH 暴露是否会影响循环 RNA 的表达尚不清楚。目前已发现几种可调控 hsa-miR-206-3p 的 circRNA。我们假设 MDI-GSH 共轭物暴露会诱导巨噬细胞中的内源性 circRNA 调节 hsa-miR-206-3p。我们使用 RT-qPCR 方法测定了经 MDI-GSH 共轭化合物处理的分化 THP-1 巨噬细胞中与 hsa-miR-206-3p 结合的候选 circRNAs 的表达。MDI-GSH 暴露诱导了 hsa_circ_0008726 及其宿主基因转录本 DNAJB6,而其他被检测的 circRNA 要么未被检测到,要么没有变化。RNA 诱导的沉默复合物免疫沉淀(RISC-IP)实验证实,hsa-miR-206-3p 能与 hsa_circ_0008726 结合。转染 hsa_circ_0008726 siRNA 或 hsa_circ_0008726 过表达质粒后,巨噬细胞中内源性 hsa-miR-206-3p、hsa-miR-206-3p 调控的 KLF4 和 KLF4 激活的 M2 巨噬相关标志物及趋化因子的表达分别受到上调或下调。这些结果表明,MDI-GSH 暴露可通过诱导内源性 hsa_circ_0008726/DNAJB6 下调 hsa-miR-206-3p,从而导致巨噬细胞中 hsa-miR-206-3p 介导的调控上调。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Cells
Cells Biochemistry, Genetics and Molecular Biology-Biochemistry, Genetics and Molecular Biology (all)
CiteScore
9.90
自引率
5.00%
发文量
3472
审稿时长
16 days
期刊介绍: Cells (ISSN 2073-4409) is an international, peer-reviewed open access journal which provides an advanced forum for studies related to cell biology, molecular biology and biophysics. It publishes reviews, research articles, communications and technical notes. Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. There is no restriction on the length of the papers. Full experimental and/or methodical details must be provided.
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