Premium
Fibroblast growth factor inducible 14 signaling facilitates anti‐dsDNA IgG penetration into mesangial cells
Author(s) -
Li Ruilian,
Jia Fangyan,
Ren Kaixuan,
Luo Mai,
Min Xiaoyun,
Xiao Shengxiang,
Xia Yumin
Publication year - 2021
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.29838
Subject(s) - internalization , hmgb1 , fibroblast , signal transduction , microbiology and biotechnology , downregulation and upregulation , cytokine , chemistry , antibody , tumor necrosis factor alpha , cancer research , mesangial cell , biology , in vitro , immunology , inflammation , receptor , biochemistry , gene
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.