| Objective:Renal tubulointerstitial fibrosis is the common final outcome of almost all progressive chronic kidney diseases.A sustained injury sets up the fibrogenic stage (priming)and triggers the activation and expansion of matrix-producing cells from multiple sources through different mechanisms, including activation of interstitial fibroblasts and pericytes, phenotypic transformation of tubular epithelial and vascular endothelial cells and recruitment of circulating fibrocytes. A variety of cellular and molecular events,such as renal tubular atrophy, microvascular rarefaction and tissue hypoxia, promote scar formation, and ensure a vicious progression to end stage kidney failure. In which,activation of the complement system is involved in the process of the tubular epithelial cells-mesenchymal transition (EMT),resulting in renal interstitial fibrosis.Recent studies have found that complement C5a receptor plays an important role in renal interstitial fibrosis.Complement C5a receptor(C5aR), which is also known as CD88,is a seven-transmembrane segment belonging to the family member of rhodopsin-like G-protein coupled receptors(GPCRs)and is the specific receptor of the anaphylatoxin C5a(cleavage products of C5complement), C5a combined with each other, and activation of C5aR,which play a biological effect.Its natural ligand is the C5a and define a C5a.Now it is considered that playing biological effect through the two binding sites, one is the N-terminal of the recognition site, another is the C-terminal of the activated site,which resulting in signal transduction.C5aR was initially thought to be expressed mainly on myeloid cells, could modulate the immune system, but now it is established that C5aR could be expressed on the kidney, some studies had shown that it expressed on renal tubular epithelial cells, than to a much higher level of expression in glomerular mesangial cells.In flammatory conditions, C5aR begin to express from proximal tubules. C5aR combine with C5a binding chemokine inducing granulocytes and lymphocytes, and the release of a variety of inflammatory cytokines, which play a role in the process of renal injury, and tubulointerstitial fibrosis are still in the preliminary study. As we all known, the zinc finger transcription factor snail was involved in renal fibrosis starting transforming growth factor(TGF-P)was a key transcription factor, promote cell migration and renal interstitial fibrosis EMT.This finding provided a link between an transcription factor and renal interstitial fibrosis.The aim of this study is to express the transcription factor Snail and tubulointerstitial fibrosis of the relationship between C5aR and zinc finger in renal tissue of patients with IgA nephropathy, The C5aR may be lead to tubulointerstitial damage by regulating Snail factor, further development tissue fibrosis, provide a theoretical basis for the pathogenesis of IgAN and delay the progress of IgAN.Methods:38cases renal tissue of IgA nephropathy patients,while peripheral blood sample were collected. According to the degree of renal fibrosis,renal sample were divieded into three groups [according to the Oxford typing,with or without glomerulosclerosis, tubular atrophy and interstitial fibrosis(TO0%-25%,T126%-50%mild to moderate to severe T2>50%)]:mild damage group(T0)in15cases, moderate damage group(T1)in15cases, and severe damage group(T2)in8cases. A control group of5cases, renal tumor patients, the kidneys removed from tumor by pathological examination results in normal kidney tissues as control object of study. Was detected by immunohistochemical method in4groups of subjects distribution in renal tissue of objects in C5aR, and expression of Snail, and analyzed by ImagePro Plus6.0pathological image, the average optical density of positive expression of calculating target; content and enzyme linked immunosorbent assay in detection of serum C5aR,Snail.At the moment, determination of blood biochemical indexes:blood ure nitrogen,serum creatinine, uric acid, blood albumin and measured24-hour urine protein and urine osmotic pressure. And statistical analyses were performed using SPSS13.0software.The measure-ment data with the mean±tandard deviation(χ±s), normal variance,by analysis of variance(ANOVA),non-normal or variance not neat by nonparametric test,multiple comparisons between groups using Kruskal-Wallis H test, Pearson correlation test, P<0.05level showed that the differences have statistical significance.Results:(1)Among the groups of the Age,Sex,BMI and ALB have no statistically significant difference.(P=0.704P=0.778P=0.767P=0.053,P>0.05).(2) The expression of C5aR and Snail in renal tissueIn the control group, C5aR and Snail in renal tubular epithelial cells and interstitial express sparse. Kidney tissue in patients with IgA nephropathy, C5aR expression is significantly enhanced, mainly locate in the cytoplasm of the renal tubular epithelial cells, interstitial fibrosis matrix area also positive expresse, glomerular mesangial cells have a small expression.C5aR expression are enhanced in the experimental group increased with the aggravation of renal interstitial fibrosis. The experimental group is mainly in the area ofrenal tubular epithelial cells and interstitial expression of Snail protein expression levels compare with the control group increasing, and Snail nuclear staine with renal interstitial fibrosis progression and increase.(3) Blood C5aR, Snail levels of correlation analysisSerum C5aR, Snail levels are with aggravation of renal interstitial fibrosis and increased, in the control group and experimental group are statistically significant(P<0.05),experimental group1and experimental group2,3had stati-stical significance(P<0.05), experimental group2,3showed no significant differrence(P>0.05).C5aR and Snail level of serum, urine protein, serum creatinine was positively correlated (correlation coefficient are r=0.896r=0.530r=0.337,P<0.01),and urine osmolality, eGFR negatively correlated (correlation coefficient of r=-0.408r=-0.534,P<0.01), no significant difference of C5aR level and blood protein (P>0.05).(4) immunohistochemistry average optical density(IOD) of the C5aR and Snail of the correlation analysisAverage optical density of C5aR(IOD) and other indicators are analyzed, find the IOD value of C5aR and IOD value of Snail, Scr, uric acid,24urinary protein positive correlation (correlation coefficients are r=0.983r=0.533r=0.399r=0.625,P<0.01), and urine osmolality, eGFR negatively correlated (correlation coefficient are r=-0.599r=-0.642,P<0.01),no statistical signify-cance with ALB, BMI(P>0.05). In addition, the IOD values of Snail are positively correlated with Scr, uric acid,24urinary protein(correlation coefficient are r=0.579R=0.423r=0.625,P<0.01), and urine osmolality, eGFR negatively correlated(correlation coefficient of r=-0.611, r=-0.653, P<0.01), and ALB, BMI had no statistical significance(P>0.05).(5) Average optical density of C5aR immunoreactivity(IOD) correlation analysis with serum level of C5aR, SnailC5aR IOD values are positively with the serum level of Snail,the serum level of C5aR correlation(correlation coefficients were r=0.878,r=0.949,P<0.01), a significant correlation.Conclusion:1In IgA patients with kidney diseases, the activation of C5aR promoter may lead to kidney EMT, which lead to renal interstitial fibrosis;2The expression level of C5aR expression with aggravation of renal interstitial fibrosis and enhancement, urine protein also increases, eGFR decrease gradually;3The expression of C5aR and Snail factor both increase, and there is an association between them(r=0.878,p<0.01), it is possible by the activation of Snail factor, the start process of the EMT,involve the development in renal interstitial fibrosis. |
PDF Full Text Request