Expression and regulation of P-selectin and MCP-1 in renal tubules of diabetic rats

Objective:To explore the dynamic expression of P-selectin,MCP-1,NF-κB and p38MAPK in the renal tubules of diabetic rats and to investigate their mutual relationship and roles in the pathogenesis of diabetic nephropathy.Methods:Streptozotozin(STZ)-induced diabetic rats were randomly divided into day 3,week 1,week 2,week 4 and week 8 groups,each group having a normal age-matched control group.Immunohistochemistry was employed to detect the expression of P-selectin,MCP-1,NF-κB,p38MAPK and fibronectin(FN) in the renal tubules.p38MAPK and I-κB proteins in the renal cortex were detected by Western blot methods.The morphological changes of renal tissues were observed under light microscopy in PAS staining sections.Blood glucose and 24 hours urine proteins were analyzed by biochemistry methods.Results:Increased renal index and urine proteins were observed from diabetes day 3.The expression of p38MAPK,NF-κB,P-selectin and MCP-1 in renal tubules were increased in diabetes day 3 and week 1 growes compared with those of the normal age-matched control group(P0.05) respectively,and thereafter the increase was more significant with development of diabetes while I-κB protein decreased.The expression of FN in renal tubules of diabetic groups was increased compared with that of the normal control group from week 2(P0.05).In diabetes week 4group,the expression of P-selectin and MCP-1 was quite remarkable,and was positively correlated with p38MAPK,NF-κB and FN expression and renal index(P0.05).Conclusion:P38MAPK and NF-κB may up-regulate the expression of P-selectin and MCP-1 in the renal tubules of diabetic rats,which play an important role in the pathogenesis of the diabetic tubulo-interstitium injury.