Although growing advances have been made in the regulation of lupus nephritis recently, lupus nephritis is still one of the major causes of death in SLE patients and the pathogenesis remains largely unknown. Therefore, exploring the pathological mechanisms is urgently needed for designing and developing novel therapeutic strategies for lupus nephritis. Human renal mesangial cells (HRMCs) were transfected with sh-NEAT1, miR-146b mimic, pcDNA-NEAT1, miR-146b inhibitor, or sh-TRAF6 to modify their expression. Lipopolysaccharide (LPS) was used to induce inflammatory injury. Cell viability was examined with CCK8. Apoptosis was determined by flow cytometry and Hoechst staining. qRT-PCR and western blot were used to analyze gene expression. The secretion of inflammatory cytokines was examined with ELISA. The bindings of NEAT1 with miR-146b and miR-146b with TRAF6 were tested by dual-luciferase reporter assay. NEAT1 was upregulated in LPS-treated HRMCs. Both the knockdown of NEAT1 and TRAF6 suppressed the LPS-induced inflammatory injury in HRMCs. NEAT1 directly targeted miR-146b to control miR-146b-mediated regulation of TRAF6 expression in HRMCs. NEAT1 promoted the expression of TRAF6 via targeting miR-146b to accelerate the LPS-mediated renal mesangial cell injury in HRMCs. Moreover, TRAF6 activated the NF-κB signaling in HRMCs. NEAT1 accelerated renal mesangial cell injury via directly targeting miR-146b, promoting the expression of TRAF6, and activating the NF-κB signaling in lupus nephritis. Our investigation elucidated novel pathological mechanisms and provided potential therapeutic targets for lupus nephritis.

中文翻译：

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LncRNA NEAT1在狼疮性肾炎中通过调节miR-146b/TRAF6/NF-κB轴加速肾系膜细胞损伤

尽管近年来狼疮性肾炎的调控取得了越来越多的进展，但狼疮性肾炎仍是导致 SLE 患者死亡的主要原因之一，其发病机制尚不清楚。因此，迫切需要探索病理机制以设计和开发新的狼疮性肾炎治疗策略。用 sh-NEAT1、miR-146b 模拟物、pcDNA-NEAT1、miR-146b 抑制剂或 sh-TRAF6 转染人肾系膜细胞 (HRMC) 以改变它们的表达。脂多糖（LPS）用于诱导炎症损伤。用CCK8检查细胞活力。通过流式细胞术和Hoechst染色确定细胞凋亡。qRT-PCR 和蛋白质印迹用于分析基因表达。用ELISA检查炎性细胞因子的分泌。NEAT1 与 miR-146b 和 miR-146b 与 TRAF6 的结合通过双荧光素酶报告基因测定进行测试。NEAT1 在 LPS 处理的 HRMC 中上调。NEAT1 和 TRAF6 的敲低均抑制了 LPS 诱导的 HRMC 炎症损伤。NEAT1 直接靶向 miR-146b 以控制 HRMC 中 miR-146b 介导的 TRAF6 表达调节。NEAT1 通过靶向 miR-146b 促进 TRAF6 的表达，以加速 HRMC 中 LPS 介导的肾系膜细胞损伤。此外，TRAF6 激活 HRMC 中的 NF-κB 信号。NEAT1通过直接靶向miR-146b，促进TRAF6的表达，激活狼疮性肾炎中的NF-κB信号，加速肾系膜细胞损伤。我们的研究阐明了新的病理机制，并为狼疮性肾炎提供了潜在的治疗靶点。