The Role of Th17/IL-17 in the Pathogenesis of Primary Nephrotic Syndrome in Children
The Role of Th17/IL-17 in the Pathogenesis of Primary Nephrotic Syndrome in Children
复制标题
DOI：
10.1159/000350161
复制
发表时间：
2013-01-01
影响因子：
2.8
通讯作者：
Tao, Hong
中科院分区：
文献类型：
--
作者：
Wang, Li;Li, Qiu;Tao, Hong
背景：本工作旨在探讨Th17和IL-17信号在儿童原发性肾病综合征（PNS）发病机制及足细胞损伤中的作用，儿童PNS分为微小病变肾病综合征（MCNS）和非微小病变肾病综合征[NMCNS，包括系膜增生性肾小球肾炎（MsPGN）和局灶节段性肾小球硬化（FSGS）]。方法：采用流式细胞术（FCM）观察Th17细胞的循环频率以及AnnexinV-FITC/PI对足细胞的凋亡情况。使用酶联免疫吸附测定法测量血清IL-1β和IL-6水平。使用直接免疫荧光方法通过 FCM 分析检查足细胞中的 Fas 和 FasL 表达。采用逆转录聚合酶链反应测定 RORc、IL-23p19、Nephrin、WT1、Synaptopodin、Podocalyxin、Fas 和 FasL 的 mRNA 表达量。免疫组化法检测肾活检组织中IL-17、IL-1β的表达。还使用免疫细胞化学测量了足细胞细胞培养物中 WT1、Caspase 8 和 Caspase 3 的表达。结果：MCNS组和NMCNS组Th17细胞循环频率、RORc和IL-23p19 mRNA水平以及血清IL-6和IL-1β水平高于对照组（均P < 0.05），且NMCNS组高于MCNS组（均P < 0.05）。 MCNS、MsPGN、FSGS组肾活检组织中IL-17、IL-1β的表达高于对照组（均P < 0.05）。重组鼠IL-17 (rmIL-17)对小鼠足细胞的Nephrin、Synaptopodin和WT1的表达没有影响，但引起足细胞萼蛋白的表达减少，并以剂量和时间依赖性的方式促进细胞凋亡。此外，rmIL-17增加了Fas、Casepase-8和Casepase-3的表达，但对FasL的表达没有影响。结论：Th17/IL-17可能通过降低足细胞萼蛋白水平、诱导足细胞凋亡参与PNS的发病。版权所有 (C) 2013 S. Karger AG，巴塞尔
Background: This work aims to explore the role of Th17 and IL-17 signaling in the pathogenesis of primary nephrotic syndrome (PNS) in children and podocyte injury, children with PNS were divided into minimal change nephrotic syndrome (MCNS) and non-minimal change nephrotic syndrome [NMCNS, including mesangial proliferative glomerulonephritis (MsPGN) and focal segmental glomerulosclerosis (FSGS)]. Methods: Flow cytometry (FCM) was used to observe the circulating frequency of Th17 cells and the apoptosis of podocytes by annexinV-FITC/PI. Serum IL-1 beta and IL-6 levels were measured using enzyme-linked immunosorbent assay. The Fas and FasL expressions in podocytes were examined by FCM analysis using a direct immunofluorescence method. Reverse transcription polymerase chain reaction was applied to measure the mRNA expressions of RORc, IL-23p19, Nephrin, WT1, Synaptopodin, Podocalyxin, Fas, and FasL. The IL-17 and IL-1 beta expression in renal biopsy tissue was detected by immunohistochemistry. The expressions of WT1, Caspase 8, and Caspase 3 in podocyte cell culture were also measured using immunocytochemistry. Results: Circulating frequencies of Th17 cells, mRNA levels of RORc and IL-23p19, and serum levels of IL-6 and IL-1 beta were higher in the MCNS and NMCNS groups than in the control group (all P < 0.05), and were higher in the NMCNS group than in the MCNS group (all P < 0.05). The expressions of IL-17 and IL-1 beta in renal biopsy tissue were higher in the MCNS, MsPGN, and FSGS groups than in the control group (all P < 0.05). Recombinant murine IL-17 (rmIL-17) had no effect on the expressions of Nephrin, Synaptopodin, and WT1 of mouse podocytes, but caused an decrease in the expression of podocalyxin as well as promoted apoptosis in a dose-and time-dependent fashion. Moreover, rmIL-17 increased the expression of Fas, Casepase-8, and Casepase-3, but had no effect on that of FasL. Conclusion: Th17/IL-17 may contribute to the pathogenesis of PNS by decreasing the podocalyxin level and inducing podocyte apoptosis. Copyright (C) 2013 S. Karger AG, Basel