Local CD34-positive capillaries decrease in mouse models of kidney disease associating with the severity of glomerular and tubulointerstitial lesions

Abstract

Background: The renal vasculature plays important roles in both homeostasis and pathology. In this study, we examined pathological changes in the renal microvascular in mouse models of kidney diseases. Methods: Glomerular lesions (GLs) in autoimmune disease-prone male BXSB/MpJ-Yaa (Yaa) mice and tubulointerstitial lesions (TILs) in male C57BL/6 mice subjected to unilateral ureteral obstruction (UUO) for 7 days were studied. Collected kidneys were examined using histopathological techniques. A nonparametric Mann-Whitney U test (P < 0.05) was performed to compare healthy controls and the experimental mice. The Kruskal-Wallis test was used to compare three or more groups, and multiple comparisons were performed using Scheffe's method when significant differences were observed (P < 0.05). Results: Yaa mice developed severe autoimmune glomerulonephritis, and the number of CD34+ glomerular capillaries decreased significantly in GLs compared to that in control mice. However, UUO-treated mice showed severe TILs only, and CD34+ tubulointerstitial capillaries were decreased significantly in TILs with the progression of tubulointerstitial fibrosis compared to those in untreated control kidneys. Infiltrations of B-cells, T-cells, and macrophages increased significantly in the respective lesions of both disease models (P < 0.05). In observations of vascular corrosion casts by scanning electron microscopy and of microfil rubber-perfused thick kidney sections by fluorescence microscopy, segmental absences of capillaries were observed in the GLs and TILs of Yaa and UUO-treated mice, respectively. Further, transmission electron microscopy revealed capillary endothelial injury in the respective lesions of both models. The numbers of CD34+ glomerular and tubulointerstitial capillaries were negatively correlated with all examined parameters in GLs (P < 0.05) and TILs (P < 0.01), respectively. Conclusions: From the analysis of mouse models, we identified inverse pathological correlations between the number of local capillaries in GLs and TILs and the severity of kidney diseases.