Renal Vascular Endothelial-mesenchymal Transition In Systemic Lupus Erythematosus Associated Thrombotic Microangiopathy

Objective:The purposes of this research are to investigate the changes of renal interstitial vascular endothelial cells phenotype,and further to explore the relation among these changes and the vascular lesion as well as renal interstitial fibrosis in those patients who suffered from systemic lupus erytnematosus with thrombotic microangiopathy(SLE-TMA).Methodology:This research included renal biopsies from 30 lupus patients who showed renal interstitial vascular TMA.Renal interstitial vascular TMA lesions were seperated into acute TMA and chronic TMA according to their pathological histomorphology by light microscopy.Normal controls were provided from the nephrectomized kidney of those patients with renal cancer.Use immunofluorescence assays to stain the CD31 and a-smooth muscle actin(a-SMA)of renal interstitial vascular endothelial cells.Use immunohistochemical assays to stain the CD31,vascular endothelial cadherin(VE-cadherin),a-SMA and transforming growth factor-β(TGF-β)of renal interstitial vascular endothelial cells.Use image analysis software Image Pro Plus 6.0 and Aperio Image Scope to analyze the expression of interstitial vascular endothelial markers quantitatively.The result was noted by the mean density(MD,integral optical density(IOD)/area of renal interstitial vascular endothelium)and the degree of renal interstitial fibrosis.Results:Images obtained from confocal immunofluorescence microscopy exhibited increased level of a-SMA expression in the renal interstitial vascular endothelial cells of SLE-TMA,while no a-SMA expression in normal group renal interstitial vascular endothelial cells.In acute TMA group,the CD31,VE-cadherin and TGF-β expression of renal interstitial vascular endothelial cells was all decreased(P<0.05),but the a-SMA expression was raised significantly(P<0.001)compared with the normal one.In chronic TMA group,the renal interstitial vascular endothelial expression of CD31,VE-cadherin and TGF-β was significantly lower and the expression of a-SMA was significantly higher than that in normal group(P<0.001).Compared with acute TMA group,the expression of CD31(P=0.02),VE-cadherin(P=0.058)and TGF-β(P<0.01)was much lower,and the expression of a-SMA was higher(P=0.09)in chronic TMA group.The MD of renal interstitial vascular endothelial CD31 expression was negatively correlated with renal interstitial fibosis(r=-0.458,P=0.011),but α-SMA expression was positively correlated with the degree of renal interstitial fibrosis(r=0.439,P=0.015).Conclusion:The transition of renal interstitial vascular endothelial cells to mesenchymal cells was discovered in SLE-TMA,and it was associated with the degree of renal interstitial fibrosis.