Expression of thrombospondin-1 and its receptor CD47 in vascular lesions of renal interstitial fibrosis

Abstract

Objective To observe the expression of TSP-1 and its receptor CD47 in unilateral ureteral obstruction (UUO) rats, and to investigate the role of TSP-1-CD47 in lesions of peritubular capillary (PTC). Methods A total of 60 Sprague-Dawley rats were randomly divided into: sham-operation group (SOR) (n=15) and UUO group (n=45). UUO group sacrifice timing consisted of three time points: 3 day, 7 day, 14 day, with 15 animals for each time point. Detection of 24h urinary protein and renal function was made by automatic biochemistry analyzer, and interstitial pathological changes were shown by Masson staining. The expression of TSP-1 and CD47 was measured by immunohistochemical and immunofluorescence double staining. Western blot was used to detect the expression of CD34, VEGF, TSP-1 protein in rat kidneys. The correlations among CD34, VEGF, and TSP-1 protein expression were analyzed with Pearson method. Results Compared with the sham-operation group, the levels of serum creatinine (Scr), blood urea nitrogen (BUN), and 24h urinary protein did not change significantly in UUO group, but features of renal tubulointerstitial fibrosis were obvious, and the score of renal interstitial lesion was significantly higher in UUO group. Immunofluorescence double staining showed that TSP-1 and CD47 were coexpressed in UUO renal tubules. Western blot confirmed that TSP-1 protein level was significantly higher in UUO group, while the expressions of CD34 and VEGF protein were decreased. Correlation analysis showed that TSP-1 protein was negatively associated with the expression of CD34 and VEGF(r=-0.931, P<0.01; r=-0.953, P<0.01). Conclusion TSP-1 and its receptor CD47 were coexpressed in UUO rats, and negatively associated with PTC. TSP-1 may be involved in the pathological changes of PTC through CD47 in UUO kidneys. Key words: Unilateral ureteral obstruction; Thrombospondin-1; CD47; Peritubular capillary lesion