Imaizumi Tadaatsu, Tanaka Hiroshi, Tajima Atsushi, Yokono Yoshikazu, Matsumiya Tomoh, Yoshida Hidemi, Tsuruga Kazushi, Aizawa-Yashiro Tomomi, Hayakari Ryo, Inoue Ituro, Ito Etsuro, Satoh Kei
Department of Vascular Biology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
Am J Nephrol. 2010;32(5):462-8. doi: 10.1159/000321365. Epub 2010 Oct 18.
BACKGROUND/AIMS: MicroRNAs are noncoding small RNA molecules that posttranscriptionally regulate gene expression. microRNA-155 (miR-155), one of the microRNAs, is involved in the control of various genes. However, the role of miR-155 in inflammatory responses in mesangial cells is not known. In the present study, we examined the expression of miR-155 in mesangial cells.
The expression of miR-155 in cultured normal human mesangial cells treated with interferon-γ (IFN-γ) and/or tumor-necrosis factor-α (TNF-α) was examined. The cells were transfected with miR-155 mimic, siRNA against transforming growth factor-β-activated kinase-1 (TAK1)-binding protein 2 (TAB2) or siRNA against nuclear factor-κB (NF-κB).
IFN-γ and TNF-α synergistically induced the expression of miR-155. Transfection of cells with miR-155 mimic inhibited the expression of TAB2 and IFN-γ-inducible protein of 10 kDa (IP-10). The expression of IP-10 was suppressed by knockdown of TAB2. Induction of miR-155 was inhibited by RNA interference against TAB2 or NF-κB.
Combined stimulation with IFN-γ and TNF-α induces miR-155 via TAB2 and NF-κB. miR-155 negatively regulates TAB2, as a negative feedback system, to lower IP-10 expression. miR-155 may play a role in the regulation of inflammatory and immune reactions in the kidney.
背景/目的：微小RNA是一类非编码小RNA分子，可在转录后水平调控基因表达。微小RNA-155（miR-155）是其中之一，参与多种基因的调控。然而，miR-155在系膜细胞炎症反应中的作用尚不清楚。在本研究中，我们检测了miR-155在系膜细胞中的表达。
检测了用干扰素-γ（IFN-γ）和/或肿瘤坏死因子-α（TNF-α）处理的培养正常人系膜细胞中miR-155的表达。细胞分别转染miR-155模拟物、针对转化生长因子-β激活激酶-1（TAK1）结合蛋白2（TAB2）的小干扰RNA（siRNA）或针对核因子-κB（NF-κB）的siRNA。
IFN-γ和TNF-α协同诱导miR-155的表达。用miR-155模拟物转染细胞可抑制TAB2和10 kDa的IFN-γ诱导蛋白（IP-10）的表达。敲低TAB2可抑制IP-10的表达。针对TAB2或NF-κB的RNA干扰可抑制miR-155的诱导。
IFN-γ和TNF-α联合刺激通过TAB2和NF-κB诱导miR-155。作为一种负反馈系统，miR-155负向调节TAB2以降低IP-10的表达。miR-155可能在肾脏炎症和免疫反应的调节中发挥作用。
