ABSTRACT
Objective To investigate the effects and mechanism of interleukin 33 (IL-33) on renal tubular injury in mice with lupus nephritis.Methods Twelve-week-old female MRL/lpr mice were randomly divided into model group,IL-33 group and solvent control group with 10 rats in each group.Ten female MRL/MP mice of the same age were used as normal control group.The mice in IL-33 group were intraperitoneally injected with 100 μL of phosphate buffer saline (PBS),containing 2 μg of recombinant mouse IL-33,once a day for 14 days.The mice in control group and the model group were intraperitoneally injected with the same dose of PBS.All the mice were sacrificed at 14 weeks of age.Serum creatinine (Cr) and urea nitrogen (BUN) concentrations were determined by serum separation.The urine in 24 hours was collected testing urinary protein creatinine ratio and urinary protein quantification.The contents of E-cadherin,α-SMA,and JAK/STAT pathway signaling proteins,including JAK2,p-JAK2,STAT1,and p-STAT1,were detected by Western blot.Results The BUN,urinary protein creatinine ratio and urine protein level of the IL-33 group were significantly higher than those of the model group (all P＜0.05).The expression of renal tubular epithelial cells o-SMA in the IL-33 group was higher than that in the model group,and the difference was statistically significant (P＜0.05).Compared with the model group,the expression of E-cadherin in the tubular epithelial cells of IL-33 group decreased and the expression of p-JAK2 and p-STAT1 protein increased,and the differences were all statistically significant (all P＜0.05).Compared with the model group,the levels of JAK2 and STAT1 in IL-33 group change little,and the differences were not statistically significant (all P＞0.05).Conclusions IL-33 can cause tubulointerstitial lesions in lupus mice,and its mechanism may be related to the activation of JAK/STAT pathway.
ABSTRACT
Purpose To investigate the role of S3I-201 on tubular interstitial lesion in lupus nephritis.Methods MRt/MpJ mice were designated as the control group.MRL/lpr nice were randomly divided into LN group,S3I-201 group and DMSO group.The serum and 24 h-urine were collected to detect the serum creatinine,blood urea nitrogen and urine protein.Immunohistochemistry was used to detect the expression of FN.Western blotting analysis was used to determine the expression of E-cadherin,α-SMA,MCP-1,ICAM1,STAT3 and p-STAT3.Results Compared with the expression level in control group,the protein level of α-SMA,MCP-1,ICAM1 and FN were increased in renal tissue of MRL/lpr mice,while the expression of E-cadherin was markedly decreased.And the STAT3 was activated in renal tissue of MRL/lpr mice.The administration of S3I-201 could inhibite the activation of STAT3 and ameliorate the expression of E-cadherin,α-SMA,MCP-1,ICAM-1 and FN.Conclusion S3I-201 can relieve the tubular interstitial leison,which maybe concerned with the phosphorylation of STAT3.