Fibroblast growth factor inducible 14 signaling facilitates anti-dsDNA IgG penetration into mesangial cells
Fibroblast growth factor inducible 14 signaling facilitates anti-dsDNA IgG penetration into mesangial cells
复制标题
成纤维细胞生长因子诱导型 14 信号传导促进抗 dsDNA IgG 渗透至系膜细胞
DOI：
10.1002/jcp.29838
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发表时间：
2021
影响因子：
5.6
通讯作者：
Yumin Xia
中科院分区：
文献类型：
--
作者：
Ruilian Li;Fangyan Jia;Kaixuan Ren;Mai Luo;Xiaoyun Min;Shengxiang Xiao;Yumin Xia
抗双链DNA（dsDNA）抗体通过触发肾细胞纤维化过程诱导系统性红斑狼疮患者的肾损伤。然而，抗dsDNA免疫球蛋白G（IgG）渗透到细胞中的确切机制仍不清楚。本研究旨在研究肿瘤坏死因子样弱凋亡诱导剂（TWEAK）/成纤维细胞生长因子诱导型14（Fn 14）信号传导对抗dsDNA IgG渗透到细胞中的影响。体外培养肾小球系膜细胞，并用TWEAK和抗dsDNA IgG刺激。结果显示，TWEAK剂量依赖性地增强抗dsDNA IgG的细胞内化和高迁移率族蛋白1（HMGB 1）的表达。此外，TWEAK和抗dsDNA IgG合成下调细胞因子信号转导抑制因子1，并诱导各种纤维化因子的表达。此外，HMGB 1的抑制减弱了TWEAK对抗dsDNA IgG内化的增强作用。HMGB 1的TWEAK上调涉及核因子-κB和磷脂酰肌醇3-激酶/蛋白激酶B途径。因此，TWEAK/Fn 14信号有助于抗dsDNA IgG的渗透和系膜细胞中的相关纤维化过程。
Anti‐double‐stranded DNA (dsDNA) antibodies induce renal damage in patients with systemic lupus erythematosus by triggering fibrotic processes in kidney cells. However, the precise mechanism underlying penetration of anti‐dsDNA immunoglubolin G (IgG) into cells remains unclear. This study was designed to investigate the effect of tumor necrosis factor‐like weak inducer of apoptosis (TWEAK)/fibroblast growth factor inducible 14 (Fn14) signaling on anti‐dsDNA IgG penetration into cells. Mesangial cells were cultured in vitro, and stimulated with TWEAK and anti‐dsDNA IgG. The results revealed that TWEAK dose‐dependently enhanced cellular internalization of anti‐dsDNA IgG and the expression of high‐mobility group box 1 (HMGB1). In addition, TWEAK and anti‐dsDNA IgG synthetically downregulate suppressor of cytokine signaling 1, and induce the expression of various fibrotic factors. Furthermore, inhibition of HMGB1 attenuates the enhancement effect of TWEAK on anti‐dsDNA IgG internalization. The TWEAK upregulation of HMGB1 involves the nuclear factor‐κB and phosphatidylinositide 3‐kinase/protein kinase B pathways. Therefore, TWEAK/Fn14 signaling contributes to the penetration of anti‐dsDNA IgG and relevant fibrotic processes in mesangial cells.