Serpin B1 Alleviates Lupus Nephritis via Modulating the Mitogen-Activated Protein Kinase Pathway

Abstract

Background: Lupus nephritis (LN) is the predominant cause of death in systemic lupus erythematosus patients, for which current therapies are ineffective and often toxic. The aim of this study was to investigate the effect and related mechanisms of serine protease inhibitor B1 (Serpin B1) in LN. Methods: Kidney samples from LN and non-LN patients were observed pathologically and pro-inflammatory cytokines were detected in serum and urine using enzyme-linked immunosorbent assays. Subsequently, the expression of Serpin B1 was analyzed using bioinformatics analysis and further validated by western blotting. In vitro, the proliferation and apoptosis of simian virus 40-MES-13 (SV40) mouse glomerular mesangial cells and mitogen-activated protein kinase (MAPK) pathway activity were examined after the knockdown of Serpin B1. In vivo, the survival rate, inflammatory response, and histology of mice in each group were examined. Results: LN patients showed glomerular injury with high Serpin B1 expression (p < 0.001). Knockdown of Serpin B1 inhibited cell proliferation and extracellular regulated protein kinases activity, promoted c-Jun N-terminal kinase, P38 activity and accelerated apoptosis in lipopolysaccharide-induced SV40 cells (p < 0.001). In vivo, Serpin B1 overexpression significantly inhibited the expression of neutrophil extracellular traps, inflammatory factors, and monocyte chemoattractant protein-1. In addition, the glomerular injury was alleviated, Immunoglobin G deposition in the glomeruli was reduced. Conclusions: Overexpression of Serpin B1 can alleviate LN, and the MAPK pathway may play a key role in this process.