Department of Pediatric Nephropathy, The First Hospital of Jilin University, China.
Department of Pediatric Nephropathy, The First Hospital of Jilin University, China.
Biochem Biophys Res Commun. 2018 Dec 9;507(1-4):100-105. doi: 10.1016/j.bbrc.2018.10.173. Epub 2018 Nov 16.
The glomerular podocytes control filtration barrier permeability in the kidney, and their disturbance underlies the pathogenesis of idiopathic nephrotic syndrome (INS), a kidney disease that predominantly occurs in children. In this study, we found that the interleukin-7 receptor (IL-7R) was induced in the glomeruli of adriamycin (ADR)-induced mouse nephropathy, a rodent model of nephrotic syndrome. In addition, IL-7R was also induced by ADR in mouse podocytes cultured in vitro. Functionally, we discovered that IL-7R activation through the stimulation of recombinant IL-7 induced apoptosis of podocytes, and moreover, IL-7 stimulation inhibited nephrin activation and caused actin cytoskeleton disorganization, indicating that IL-7 stimulation induces podocyte injury. Furthermore, IL-7 stimulation impaired the filtration barrier function of podocyte monolayer. Together, these results identify IL-7 and its receptor IL-7R as potential regulators of podocyte function, which might offer a novel therapeutic target in the treatment of INS.
肾小球足细胞控制肾脏滤过屏障的通透性，其功能紊乱是特发性肾病综合征（INS）的发病基础，INS 是一种主要发生在儿童中的肾脏疾病。在这项研究中，我们发现白细胞介素 7 受体（IL-7R）在阿霉素（ADR）诱导的肾病小鼠模型的肾小球中被诱导产生，ADR 也可以在体外培养的小鼠足细胞中诱导 IL-7R 的产生。功能研究表明，通过重组白细胞介素 7（recombinant IL-7）刺激激活 IL-7R 可诱导足细胞凋亡，此外，IL-7 刺激可抑制nephrin 的激活并导致肌动蛋白细胞骨架紊乱，表明 IL-7 刺激可诱导足细胞损伤。此外，IL-7 刺激会损害足细胞单层的滤过屏障功能。总之，这些结果表明白细胞介素 7 及其受体 IL-7R 可能是足细胞功能的潜在调节因子，为 INS 的治疗提供了新的治疗靶点。
