Inflammatory Cells Infiltration In Renal Interstitial And Expression Of NF-κB, MCP-1 And OPN In Renal Tubular Cells In Human Diabetic Nephropathy

Objective:As an important chronic complication in Diabetes,diabetic nephropathy(DN)is worldwide a leading cause of end-stage renal failure.Recent studies emphasized tubulointerstitial injury as a mediator of progression of DN,and most experimental evidence links the progression of DN to tubulointerstitial inflammatory response and leukocytic cell infiltrates.Nuclear factor-κB(NF-κB)is a key transcription factor modifying the expression of inflammatory genes,such as monocyte chemoattractant protein-1(MCP-1)and Osteopontin(OPN).The present study identified the morphological changes,macrophage infiltration,and the expression changes in inflammatory factor,such as NF-κB,MCP-1,OPN,in patients with diabetic nephropathy,and investigated the correlation between these inflammatory factors expression and the clinic-pathological findings,to better understand the mechanisms of inflammation in progressive diabetic nephropathy.Method:23 patients with DN and 10 patients with renal carcinoma who underwent nephrectomy admitted our hospital between 2006 and 2007 were assorted into ADA group and control group,respectively.Clinical presentation,such as urinary Nacetylglucosaminedase (NAG),BE the levels of blood glucose and proteinuria,and pathological or immunohistochemical findings for the expression in NF-κB,MCP-1, OPN,and FN were assembled and their relations were analyzed.Results:1.The renal pathological findings showed that nonspecific tubulointerstitial change was found in control group.In contrast,among all 23 patients with DN,the inflammation responses were apparent,such as granular degeneration and focal wither in tubular epithelial cell,infiltration of inflammatory cells,interstitial fibrosis,thickened-wall and narrowed-Lumina in arteriole,which directly related to the level of proteinuria.(r=0.875,P＜0.01).2.Immunohistochemistry and in situ hybridization assay showed no NF-κB expression in control group.In contrast,the expression in NF-κB p50/p65,and NF-κB p65 mRAN increased dramatically in DN group,and their expressions were correlated significantly with the levels of proteinuria. 3.Immunohistochemistry assay showed no expression in MCP-1,OPN,and FN.In DN group,MCP-1,OPN located in renal tubular epithelial cell,and FN,in renal interstitial.The tubular expressions in MCP-1 and OPN were correlated significantly with FN,NF-κB p65,and the levels of proteinuria.4.Correlation analysis showed that there was a positive correlation between the expressions in NF-κB p65,MCP-1,OPN and the levels of serum creatinine,fasting blood-glucose,and urinary NAG.Conclusion:Our data indicate inflammation response was apparent in tubulointerstitial in patients with DN,which aggravated gradually following the renal function deterioration.Inappropriate induction of inflammatory fators such asNF-κB p65,MCP-1,OPN may be involved in the progression of DN.