MicroRNA-26a negatively regulates toll-like receptor 3 expression of rat macrophages and ameliorates pristane induced arthritis in rats

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• 作者：Congshan Jiang (1) (2)
  Wenhua Zhu (1) (2)
  Jing Xu (1) (2)
  Bo Wang (1) (2)
  Weikun Hou (3)
  Rui Zhang (3)
  Nannan Zhong (1) (2)
  Qilan Ning (1) (2)
  Yan Han (1) (2)
  Hongchuan Yu (4)
  Jian Sun (1) (2)
  Liesu Meng (1) (2)
  Shemin Lu (1) (2) (5)
  
• 刊名：Arthritis Research & Therapy
• 出版年：2014
• 出版时间：February 2014
• 年：2014
• 卷：16
• 期：1
• 全文大小：
• 作者单位：Congshan Jiang (1) (2)
  Wenhua Zhu (1) (2)
  Jing Xu (1) (2)
  Bo Wang (1) (2)
  Weikun Hou (3)
  Rui Zhang (3)
  Nannan Zhong (1) (2)
  Qilan Ning (1) (2)
  Yan Han (1) (2)
  Hongchuan Yu (4)
  Jian Sun (1) (2)
  Liesu Meng (1) (2)
  Shemin Lu (1) (2) (5)
  
  1. Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi鈥檃n Jiaotong University Health Science Center, West Yanta Road No.76, Xi鈥檃n, Shaanxi, 710061, PR China
  2. Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi鈥檃n Jiaotong University, Xi鈥檃n, Shaanxi, PR China
  3. Department of Bone and Joint Diseases, Hong Hui Hospital, Xi鈥檃n Jiaotong University Health Science Center, Xi鈥檃n, Shaanxi, 710054, PR China
  4. Department of Respiratory Medicine, Xi鈥檃n Children Hospital, Xi鈥檃n, Shaanxi, 710003, China
  5. Department of Epidemiology and Health Statistics, School of Basic Medical Sciences, Xi鈥檃n Jiaotong University Health Science Center, Xi鈥檃n, Shaanxi, China
  
• ISSN：1478-6354

文摘

Introduction Abnormal toll-like receptor (TLR)3 signaling plays an indispensable role in pathogenesis of both experimental and human rheumatoid arthritis, and microRNAs (miRNAs) might orchestrate this signaling pathway. This study was performed to determine the relationship between miR-26a and TLR3 in rat macrophages and to observe effects of miR-26a mimic on pristane induced arthritis (PIA) in rats. Methods Dual luciferase reporter assay was used to validate the direct interaction between miR-26a (a candidate miRNA to target tlr3 mRNA) and tlr3 3鈥睻TR. MiR-26a regulation on TLR3 gene expression was determined using RT-qPCR and Western blotting after miR-26a mimics and inhibitors were transfected into rat macrophage line NR8383 cells. Poly I:C (TLR3 ligand) was used to trigger TLR3 activation, and mRNA expression of its downstream cytokines interferon (ifn)-尾 and tumor necrosis factor (tnf)-伪 was accordingly detected to determine the regulation of TLR3 signaling. Expressions of TLR3 and miR-26a were detected during rat bone marrow derived macrophage (BMDM) induction, in pristane stimulated NR8383 cells and spleens from methotrexate (MTX) treated PIA rats. A miR-26a mimic was administrated intraperitoneally to PIA rats, and arthritis severity was evaluated by macroscopic or microscopic observations. Results Direct target relationship between miR-26a and tlr3 mRNA in rats was confirmed. Modifications of miR-26a function by transfection of miR-26a mimics and inhibitors exhibited corresponding repression and augmentation of TLR3 and its signaling downstream cytokine expressions in NR8383 cells. The alteration of miR-26a expression was negatively related with TLR3 expression during BMDM induction, in pristane-primed NR8383 cells and PIA rat spleens. Moreover, both abnormal expressions were rescued in MTX treated arthritis rat spleens. The miR-26a mimic treatment displayed the depression of TLR3 expression and ameliorated the disease severity in the rats with pristane induced arthritis. Conclusions MiR-26a negatively regulates TLR3 signaling via targeting of TLR3 itself in rat macrophages, and this finding provides a novel insight into abnormal TLR3 overexpression during experimental arthritis.