Relationship between expression of Smad6 and Smad7 and renal tubulointerstitial injury following unilateral ureteral obstruction in rats

Objective To investigate the relationship between the expressions of Smad6 and Smad7 and renal tubulointerstitial injury in rats with unilateral ureteral obstruction. Methods Thirty two rats were subjected to unilateral ureteral obstruction (UUO) or sham operation and then sacrificed on day 3, 7, 14 and 21 postoperatively. The levels of TGF β 1 mRNA were measured with RT PCR. The expression sites and levels of Smad6 and Smad7 were examined with immunohistochemical staining and western blot respectively. The apoptosis of renal tubular cell(RTC)was measured with in situ detection of nuclear DNA fragmentation. The diameters of tubular cell and glomerular capillary capsule(GCC)were quantitated with histomorphometry. Renal fibrosis was assessed by the determination of tissue hydroxyproline content. Results Compared with controls, the expression of TGF β 1 mRNA was significantly increased in UUO rats, and progressive tubular cell apoptosis, tubular and glomerular atrophy, and increased hydroxyproline content were observed at the same time. Immunohistochemistry indicated that Smad6 and Smad7 were expressed in both the glomeruli and proximal renal tubular cells. The expressions of Smad6 and Smad7 were significantly reduced from day 3 to 21 after UUO, which was significantly correlated to the down regulation of Anti-Smad and renal tubulointerstitial injury. Conclusion These results indicate that TGF β 1 signaling is involved in the process of renal tubulointerstitial injury after obstruction, the down regulation of these anti Smads may be the major cause of the exacerbation of renal injury in this model