Effect of interlukin-22 antibody on diabetic nephropathy via inhibition on Snail1 expression / 中国病理生理杂志

ABSTRACT

AIM:To investigate the effect of interlukin-22(IL-22)on diabetic nephropathy(DN)and its possible mechanism.METHODS: C57BL/6 mice were randomized to normal control(NC)group,DN group, DN+recombinant IL-22(rIL-22)group and DN+IL-22 antibody(anti-IL-22)group.After successful establishment of diabetes model for 8 weeks,the mice in DN+rIL-22 group and DN+anti-IL-22 group were intraperitoneally injected with rIL-22(200 μg/kg)and anti-IL-22(200 μg/kg),respectively,and the mice in NC group and DN group were intraperito-neally injected with 0.1%bovine serum albumin,twice a week for 4 weeks.After the intervention,blood glucose,kidney function,24 h urine microalbumin(m-Alb)and 24 h urine creatinine(Ucr)were measured.The pathological changes of renal tissues were observed under light microscope.The mRNA expression of Snail1 was detected by qPCR.The protein levels of fibronetin(FN)and E-cadherin were determined by Western blot.RESULTS:After the intervention,the ratio of 24 h m-Alb/Ucr increased significantly in other model groups compared with NC group(P<0.05).The levels of 24 h m-Alb and 24 h Ucr increased significantly in DN +rIL-22 group compared with DN group(P<0.05).However,in DN+anti-IL-22 group,the levels of 24 h m-Alb,24 h Ucr and 24 h m-Alb/Ucr ratio were significantly lower than those in DN group and DN+rIL-22 group(P<0.05).The tubular epithelial cell vacuolar degeneration,protein cast formation and glo-merular mesangial expansion in the renal tissues from diabetic mice were observed under light microscope.The lesions were more severe in DN+rIL-22 group,but attenuated in DN+anti-IL-22 group.The mRNA expression of Snail1 increased sig-nificantly in diabetic mice(P<0.05),but decreased significantly after a 4-week intervention by anti-IL-22(P<0.05). The expression of FN,an extracellular matrix protein,increased significantly in DN +rIL-22 group(P<0.05).The ex-pression of E-cadherin,an epithelial-mesenchymal transition marker,decreased significantly in DN +rIL-22 group as well (P<0.05).CONCLUSION: IL-22 neutralizing antibody may attenuate microalbuminuria and delay the progression of DN via inhibition of Snail1 expression in the renal tubular epithelial cells.