Expression Of Smad7 In Patients At Different Stages Of Type 2 Diabetic Nephropathy

ObjectiveDiabetic nephropathy(DN) is one of the most common microvascular complications of diabetes mellitus(DM), it is the main reason of death due to end-stage renal disease and DM. The pathogenesis of DN is not clear, transforming growth factor B(TGF-B) and its receptor(smad) pathway play an important role in DN. Suffer from DM, high glucose in blood, advanced glycation ends(AGEs) and angiotensinⅡcan activate the TGF-B/smad pathway. The activation of TGF-β/smad pathway can increase the expression of TGF-β,smad2/smad3 and smad4,and it has several effect on DN: firstly, the activation of TGF-B/smad pathway can activate tubular epithelial cells to mesenchymal cell transdifferentiation, which involved in the process of renal interstitial fibrosis; secondly, the increased expression of TGF-β,smad2/smad3 and smad4 can hasten the progressive accumulation of extracelluar matrix(ECM), participate in the process of glomerular scelrosis;finally, the activation of TGF-β/smad pathway can lead to glomerular podocytes hypertrophy, apoptosis, structural change and the glomerular basement membrane thickening; in addition, TGF-B can significantly increase the generation of monocyti chemoattractant protein-1,which can increase the permeability to albumin of glomerular podocyte. The increased expression of smad7 can inhibite the expression of smad2/smad3 and smad4,decrease the effect of the TGF-B/smad pathway activation to DN.This study is to observe the smad7 level in urine of DN patients in different stage, discuss the effect of TGF-B/smad pathway to DN.Material and MethodDivide the 87patients with type 2 diabetes mellitus(T2DM) into 3 groups according to the UAER (urinary albumin to creatinine ratio, ACR):group 1(A group) is the patients with normal albumin level of urine(38 people), group 2(B group) is the patients with microalbuminuria(29 people), group 3(C group) is the patients with clinical albuminuria(20 people). There is another group (N group) consist of healthy people without T2DM or albuminuria. To test and compare the level ofsmad7,FBG and connective indicators in different groups.ResultsThe smad7 level of group A,B and C are higher than that of group N, there are significant difference of smad7 level between any of the two groups (P＜0.01, P＜0.01, P＜0.01), the change of smad7 is the same with ACR. The FBG of group A,B and C are higher than that of group N (P＜0.01, P＜0.01, P＜0.01), but there is no statistic difference between group A,B and C (P>0.05).The age between any group is no statistic difference (P>0.05).The time patients suffer from DM of group C is longer than that of group A and B, but that between group A and B is no statistic defference (P>0.05).The BMI of group A,B and C is higher than that of group N (P＜0.01, P＜0.01, P＜0.01), but that between group A,B and C has no statistic defference (P>0.05). The results shows that BMI and high glucose in blood is relative to the change of smad7 level in urine (r=0.28, P＜0.01; r=0.43, P＜0.01)ConclusionPeople with T2DM have a higher level in urine of smad7 than healthy people, and the change of smad level is consistent with that of albuminuria, FBG is relative with the smad7 level in urine, we can infer that the TGF-β/smad pathway is activated in T2DM patients, and we confirm the view that high glucose in blood can activate the TGF-B/smad pathway.