The Expression And Significance Of Thrombospondin-1 And Vascular Endothelial Growth Factor In The Process Of Renal Interstitial Fibrosis

Objective: To elucidate the association of renal tubulointerstitial expression of TSP-1 and VEGF with renal disease in patients with chronic nephropathy and to evaluate the role of TSP-1 and VEGF in the genesis of chronic renal interstitial fibrosis. Methods: According to the score of the renal interstitial pathology injury (referring to the standard classification of the glomerular pathology by WHO in 1982), Forty-eight biopsies from patients with chronic renal disease respectively were divided into three groups: 18 patients in light injury group (score=1 to 4), 19 patients in middle injury group (score=5 to 8), 11 patients in severe injury group (score=9 to 12). And five normal specimens which were non-tumor renal tissue were surgically removed from five renal tumor patients respectively as normal control: 5 patients in the control group (score=0). All specimens were examined expression of TSP-1, VEGF, CD34, TGF-?1, α-SMA, and type IV collagen by immunohistochemisty and computer image analysis system. Results: (1) TSP-1 was not detected in normal control group, and the expression was increased gradually in other groups with the degree of renal interstitial pathological injury (P<0.01). TSP-1 was observed in tubulointerstitial space with severe lesion, with the most prominent in tubular epithelial cells, next tubulointerstitial spaces. A significant positive correlation was found between the expression of TSP-1 and the degree of renal tubulointerstitial pathological injury (r=0.861). (2) The expression of VEGF and CD34 was the strongest in tubular epithelial cells and peritubular capillaries respectively in normal control group, and decreased gradually with the degree of renal interstitial pathological injury (P≤0.01), and A significant negative correlation was found between the expression of VEGF and CD34 and the degree of renal tubulointerstitial pathological injury(r=-0.715, -0.672, respectively). (3) TGF-?1 and α-SMA were detected in normal control group, and the expression was increased gradually in other groups with the degree of renal tubulointerstitial pathological injury (P<0.01), TGF-?1 was mainly expressed in the cytoplasm of tubular epithelial cells and tubulointerstitial fibroblasts. A significant positive correlation was found between the expression of TGF-?1, α-SMA and the degree of renal tubulointerstitial pathological injury (r=0.674, 0.779 respectively). (4) The expression of type IV collagen in renal tissue of light injury group and middle injury group was significantly higher than that of normal control group (P<0.05). A significant positive correlation was found between the expression of the renal interstitial expression of type IV collagen and the degree of renal interstitial pathological injury (r=0.784). Conclusion: (1) TSP-1 was chiefly expressed in tubular epithelial cells and lesion tubulointerstitial area, especially in inflammation and fibrosis area, and increased with the degree of the renal interstitial pathological injury; while VEGF was chiefly expressed in tubular epithelial cells and podocytes, CD34 was mainly expressed in peritubular capillaries, and both decreased gradually with the degree of renal interstitial pathological injury. (2) A significant positive correlation was found between the expression of TSP-1 and the degree of renal interstitial pathological injury, While a significant negative correlation was found between the expression of VEGF and the degree of renal interstitial pathological injury. The disturbance of TSP-1 and /or VEGF expression had something to do with the ECM degradation, and contributed to the formation of renal fibrosis, by decreasing sums of peritubular capillaries.