Fibroblast growth factor inducible 14 signaling facilitates anti‐dsDNA IgG penetration into mesangial cells. Issue 1 (15th June 2020)

• Record Type: Journal Article
• Authors: Li, Ruilian; Jia, Fangyan; Ren, Kaixuan; Luo, Mai; Min, Xiaoyun; Xiao, Shengxiang; Xia, Yumin
• Is Part Of: Journal of cellular physiology. Volume 236:Issue 1(2021)
• Page Start: 249
• Page End: 259
• Publication Date: 2020-06-15
• Subjects: anti‐dsDNA IgG -- Fn14 -- HMGB1 -- lupus nephritis -- TWEAK; Physiology -- Periodicals; Cell physiology -- Periodicals; 571.6
• DOI: 10.1002/jcp.29838
• Languages: English
• ISSNs: 0021-9541

Abstract

Abstract: 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. Abstract : TNF‐like weak inducer of apoptosis/Fn14 activation facilitates the penetration of anti‐double‐stranded DNA immunoglobulin G into kidney cells. High‐mobility group box 1 mediates such effect of Fn14 signaling.