CXCL13 Involved In Lupus Nephritis By Promoting The Proliferation Of Mesangial Cells

Objective Systemic lupus erythematosus(SLE)is a common autoimmune disease in clinical.Lupus nephritis(LN)is a serious complication of SLE.Researchs at home and abroad have shown that chemokine CXCL13 may be involved in the pathogenesis of SLE.To further investigate the internal relationship between CXCL13 and SLE or LN,the present study aimed to detect serum concentration of CXCL13 in SLE patients and healthy controls.The biological effects of CXCL13 on renal mesangial cells were observed in vitro.In order to provide new basis for diagnosis and treatment of SLE or LN,we explored the potential mechanisms on cellular and molecular level.Methods 1.70 patients who were diagnosed with SLE were randomly selected as the experimental group.By renal involvement,the patients were grouped into 34 with lupus nephritis and 36 without.32 healthy individuals who kept normal physiological and biochemical index were assigned as control group.Collect the clinical information and serum of the objects above.Test serum CXCL13 levels of all objects by enzyme-linked immunosorbent assay(ELISA)and analyze the statistical differences.2.Treat human renal mesangial cells(HRMCs)with recombinant human CXCL13 in vitro to observe the changes of cells.Determine the proliferative activity of the cells by cell counting kit-8 assay(CCK8),the distribution of the cell cycle by flow cytometry(FCM)and posssible signaling pathways by western blot and immunofluorescence.3.Further investigate the possible mechanism of changes in the cells through transfection technology.Results 1.The serum concentration of CXCL13 in SLE patients was higher than that of the healthy controls [(517.04±552.34)pg/ml vs.(135.24±134.23)pg/ml,P<0.001].Particularly,the concentrations of patients with LN were even higher than those without [(702.40±710.97)pg/ml vs.(341.97±244.81)pg/ml,P=0.008].The difference was statistically significant.2.CXCL13 could promote the proliferation of HRMCs,inducing activation of the extracellular signal-regulated kinase(ERK1/2),and the phosphorylation levels of ERK1/2 increased over time.3.Normal mesangial cells expressed a certain amount of CXCR5.After CXCL13 stimulation,the expression of CXCR5 increased.When we silenced the expression of CXCR5 by siRNA,the proliferation of HRMCs weakened and the phosphorylation levels of ERK1/2 decreased.Conclusions The results of our study elaborated that high expression of CXCL13 in SLE patients especially in LN patients was clear.It might be involved in lupus nephritis by promoting the proliferation of mesangial cells in combination with CXCR5 and leading to activation of the downstream signaling pathways.Therefore,CXCL13 was expected to become a new biomarker of SLE,possibly even as a predictor of renal injury in SLE.Block CXCL13-CXCR5 and ERK pathway would become a new therapeutic target for LN.