MiR-100-3p and miR-877-3p regulate overproduction of IL-8 and IL-1β in mesangial cells activated by secretory IgA from IgA nephropathy patients
MiR-100-3p and miR-877-3p regulate overproduction of IL-8 and IL-1β in mesangial cells activated by secretory IgA from IgA nephropathy patients
复制标题
MiR-100-3p 和 miR-877-3p 调节 IgA 肾病患者分泌型 IgA 激活的系膜细胞中 IL-8 和 IL-1β 的过度产生
DOI：
10.1016/j.yexcr.2016.08.011
复制
发表时间：
2016-10-01
影响因子：
3.7
通讯作者：
Liu, Zhangsuo
中科院分区：
文献类型：
--
作者：
Liang, Yan;Zhao, Guoqiang;Liu, Zhangsuo
IgA肾病（IgAN）是原发性肾小球肾炎最常见的类型，其特征是致病性IgA在系膜沉积和系膜细胞损伤。我们前期的研究表明，分泌型IgA（SIgA）在IgAN的发病机制中发挥着重要作用，miR-16参与了IgAN患者SIgA介导的系膜细胞破坏过程。我们目前的研究旨在研究 miRNA 在 IgAN 患者的 SIgA 对系膜细胞的影响中的作用。进行MicroRNA微阵列和细胞因子测定，以获得来自IgAN患者的SIgA刺激的人肾系膜细胞（P-SIgA）中的差异microRNA表达谱，并以来自健康受试者的SIgA处理的细胞（N-SgA）作为对照。通过定量 RT-PCR 验证了微阵列分析中差异最显着的 microRNA。其中，本研究选择miR-100-3p和miR-877-3p来预测与细胞因子检测相关的靶基因。选择了 56 个差异表达的 microRNA，并对变化最显着的 17 个 microRNA 进行了验证。与N-SIgA相比，P-SIgA增加了白细胞介素（IL）-1β、IL-8、单核细胞趋化蛋白-1和转化生长因子-β1的产生。此外，我们首次证明SIgA诱导的IL-8的过量产生是通过系膜细胞中miR-100-3p的下调表达来调节的。类似地，IL-1β 的过量产生是通过 miR-877-3p 的下调表达来调节的。我们的研究结果代表了 P-SIgA 激活的人系膜细胞中的致病性 microRNA 表达谱。此外，我们提供了一种新的解释，描述了 P-SIgA 触发的系膜细胞中负责调节 IL-1 β 和 IL-8 产生的分子机制。 (C) 2016 Elsevier Inc. 保留所有权利。
IgA nephropathy (IgAN) is the most common type of primary glomerulonephritis, characterized by mesangial deposition of pathogenic IgA and the injury to mesangial cells. Our previous studies indicate that secretory IgA (SIgA) plays an important role in the pathogenesis of IgAN, and miR-16 is involved in destructive process in mesangial cells mediated by the SIgA from IgAN patients. Our current study aimed to study the role of miRNAs in the effect of SIgA from IgAN patients on mesangial cells. MicroRNA microarray and cytokines assay were performed to obtain the differential microRNAs expression profile in human renal mesangial cells stimulated by SIgA from IgAN patients (P-SIgA) with the cells treated by SIgA from healthy subjects (N-SgA) as control. The microRNAs with the most significant differences in microarray analysis were validated by quantitative RT-PCR. Among them, miR-100-3p and miR-877-3p were selected to predict target gene related to cytokines detecting in this study. Fifty-six differentially expressed microRNAs were chosen and 17 microRNAs with the most prominent changes were validated. Compared with N-SIgA, P-SIgA increased the production of interleukin (IL)-1 beta, IL-8, monocyte chemotactic protein-1 and transforming growth factor-beta 1. In addition, we for the first time demonstrated that over-production of IL-8 induced by the SIgA was regulated by down-expression of miR-100-3p in mesangial cells. Similarly, IL-1 beta over-production was regulated by down-expression of miR-877-3p. Our findings represent a pathogenic microRNAs expression profiling in human mesangial cells activated by P-SIgA. Furthermore, we provide a new explanation characterizing the molecular mechanism responsible for the regulation of IL-1 beta and IL-8 production in P-SIgA-triggered mesangial cells. (C) 2016 Elsevier Inc. All rights reserved.