The Expression And Significance Of Tissue Transglutaminase (tTG) And Connective Tissue Growth Factor(CTGF) In Kidneys From Rats With Tubulointerstitial Fibrosis

Objective: To observe the expression and co-locolization of tissue transglutaminase (tTG) and connective tissue growth factor(CTGF) in kidneys from rats with tubulointerstitial fibrosis. Methods: The animal models of unilateral ureteral obstruction(UUO) were used. The rats were randomly devided into sham-operation group (n=5), UUO group (n=6), and UUO treated with Enalapril group (n=6), A&A group(n=6). All the rats were sacrificed in 9 days, the kidneys were collected, and renal interstitial fibrosis was examined by PAS staining. The expression and localization of tTG, CTGF, and Fibronectin (FN) in the obstructed kidneys were detected by immunohistochemistry staining. The protein levels of tTG and CTGF of the whole kidney homogenates were determined by Western blot analysis. Results: Weak signals of tTG, CTGF, and FN-positive immunostaining were observed at renal tubular cells and tubulointerstitium, and very rare positive signals were seen at the glomeruli in thesham-operation group. However, much intensive signals of tTG, CTGF, and FN-positive immunostaining were observed at renal tubular cells and tubulointerstitium in UUO group, and the intensity of signals were decreased in UUO treated with Enalapril group and A&A group. Co-localization of tTG and CTGF immunoreactivity were observed at tubulointerstitium in UUO group. The levels of tTG and CTGF protein analysized by Western blotting were increased remarkably in the UUO group compared with the sham-operation group (P<0.05), and a significantly reduction of tTG and CTGF protein levels (PO.05) were presented in UUO treated with Enalapril group compared with the UUO group. The levels of tTG protein had positive correlation with the levels of CTGF protein (r=0.683, PO.05), and with the semi-quantitative levels of FN expression (r=0.737, P<0.05). Conclusion: Both of the tTG and CTGF may have concordant role in the pathogensis of renal tubulointerstitial fibrosis, Enalapril and A&A may suppress the development of fibrosis partially via down-regulation of tTG and CTGF expression.