[Effect of antisense-tissue inhibitor of metalloproteinase-1 gene transfer on tubulointerstitial lesion in rats with unilateral ureteral obstruction].
OBJECTIVE
To observe the effect of antisense- human tissue inhibitor of metalloproteinase-1 (hTIMP-1) on tubulointerstitial lesion induced by unilateral ureteral obstruction (UUO).


METHODS
Forty-two SD rats, divided into 3 groups equally, underwent UUO and received intra-ureteral injection of normal saline, empty retroviral vectors and recombinant retroviral vectors containing antisense- hTIMP-1 respectively, and were sacrificed 3 and 7 days after the operation. The expression of antisense h-TIMP-1 in rat kidney was detected by RT-PCR. Immunohistochemistry was used to detect the expression of rat TIMP-1, alpha-SMA actin (alpha-SMA), and proliferating cell nucleus antigen (PCNA) in tubulointerstitium. The relative area of renal tubulointerstitium was calculated.


RESULTS
The expression of antisense-hTIMP-1 mRNA was detected in rat renal tubulointerstitum. The expressions of rat TIMP-1, alpha-SMA and PCNA were lower in the obstructed kidneys of rats treated with antisense-hTIMP-1 than those in the rats in empty vectors group and normal saline group (3 day after: 0.75 +/- 0.07 vs 1.18 +/- 0.12, 1.14 +/- 0.14, P < 0.05; 7 days after: 2.02 +/- 0.16 vs 4.07 +/- 0.57, 4.13 +/- 0.60, P < 0.01). The relative area of renal tubulointerstitium in rats treated with antisense-hTIMP-1 was smaller than those in the empty vetors group and normal saline group (3 days after: 6.0 +/- 0.7 vs 8.2 +/- 1.2, 8.2 +/- 1.3, P < 0.01; 7 days after: 16.2 +/- 1.0 vs 21.2 +/- 2.6, 21.0 +/- 2.4, P < 0.01). More renal tubules were dilated, infiltration of inflammatory cells was seen focally or diffusely, and the relative area of renal tubulointerstitium was smaller in the antisense-hTIMP-1 group than in the empty vectors group and normal saline group. No difference was seen among the degrees of dilation/atrophy of renal tubules and infiltration of inflammatory cells in the three groups. No difference was seen between the relative area of renal tubulointerstitium in empty vectors group and normal saline group.


CONCLUSIONS
Antisense-hTIMP-1 may have beneficial effects on the tubulointerstitial lesion of obstructive nephropathy through inhibiting the expression of TIMP-1 in tubulointerstitum and the proliferation of interstitial and tubular cells.
Department of Nephrology, General Hospital of Chinese People's Liberation Army, Beijing 100853, China.
Jianping
J
Dong
Xiangmei
X
Chen
Quanzhou
Q
Feng
Bo
B
Fu
Yue
Y
Tian
Zhaoxia
Z
Wang
Hongli
H
Lin
D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D018014:Gene Transfer Techniques; D006801:Humans; D009395:Nephritis, Interstitial / Q000188:drug therapy* / Q000235:genetics; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000037:antagonists & inhibitors* / Q000235:genetics; D014517:Ureteral Obstruction / Q000188:drug therapy* / Q000235:genetics
D016376:Oligonucleotides, Antisense; D019715:Tissue Inhibitor of Metalloproteinase-1