期刊
JOURNAL OF CELLULAR PHYSIOLOGY
卷 236, 期 1, 页码 249-259出版社
WILEY
DOI: 10.1002/jcp.29838
关键词
anti-dsDNA IgG; Fn14; HMGB1; lupus nephritis; TWEAK
资金
- Innovation Capability Support Plan of Shaanxi Province [2019TD-034]
- National Natural Science Foundation of China [81874241]
The study shows that TWEAK and anti-dsDNA IgG enhance the cellular internalization of antibodies and induce the production of fibrotic factors in mesangial cells. Moreover, TWEAK regulates HMGB1, NF-κB, and PI3K/Akt pathways, promoting the penetration of antibodies.
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-kappa B 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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据