Fibroblast growth factor inducible 14 signaling facilitates anti-dsDNA IgG penetration into mesangial cells

Ruilian Li; Fangyan Jia; Kaixuan RenMai LuoXiaoyun MinShengxiang XiaoYumin Xia

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Fibroblast growth factor inducible 14 signaling facilitates anti-dsDNA IgG penetration into mesangial cells

机译：纤维母细胞生长因子诱导14信号促进anti-dsDNA免疫球蛋白渗透系膜细胞

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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 cy-tokine 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-kappaB 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.

机译：Anti-double-stranded DNA (dsDNA)诱导的抗体系统性红斑狼疮患者的肾损害狼疮通过触发纤维化的过程肾脏细胞。潜在的渗透anti-dsDNAimmunoglubolin G(免疫球蛋白)进入细胞仍然存在不清楚。肿瘤坏死因子的影响微弱细胞凋亡的诱导物(调整)/纤维母细胞生长因子诱导14 (Fn14)信号anti-dsDNA免疫球蛋白渗透进入细胞。体外细胞培养和刺激调整和anti-dsDNA免疫球蛋白。调整剂量依赖性增强细胞的内化anti-dsDNA免疫球蛋白和高机动组的表达盒1 (HMGB1)。此外,调整和anti-dsDNA免疫球蛋白综合表达下调的抑制cy-tokine信号1,诱导表达各种纤维的因素。增强抑制HMGB1变弱调整对anti-dsDNA免疫球蛋白内化。涉及到核factor-kappaB和phosphatidylinositide 3-kinase /蛋白激酶B通路。导致的渗透anti-dsDNA免疫球蛋白和相关的间质纤维化过程细胞。

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来源
《Journal of cellular physiology.》 |2021年第1期|249-259|共11页
作者
Ruilian Li; Fangyan Jia; Kaixuan RenMai LuoXiaoyun MinShengxiang XiaoYumin Xia;
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作者单位

Department of Dermatology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China;

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正文语种英语
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关键词
Fibroblast Growth Factors; HMGB1 Protein; Kidney Mesangial CellsImmunoglobulin Ganti-IgGLupus Nephritis;

机译：成纤维细胞生长因子;HMGB1蛋白;肾脏性肾炎;

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Fibroblast growth factor inducible 14 signaling facilitates anti-dsDNA IgG penetration into mesangial cells

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