The Expression Of TIMP-1 In Tubulointerstitial Lesion And The Tretment Of Obstructive Nephropathy With Kidney-targeted Antisense-TIMP-1 Gene Transfer

Objective: To explore the role of tissue inhibitor ofmetalloproteinase-1 (TIMP-1) in the renal tubulointerstitalfibrosis induced by unilateral ureteral obstruction (UUO ). Methods:Rats were sacrificed at 1, 3, 5, 7 or 14 days after UUO or sham-surgey.The protein expression of TIMP-1, α-Smooth muscle actin (α-SMA) andproliferating cell nucleus antigen (PCNA) in tubulointerstitium weredetected by immunohistochemistry at each time point. Rusults: TIMP-1expression in renal tubulointerstitum increased progressively in timestarting from 24 hours post-ligation. Interititial and some tubularcells expressed TIMP-1 from day 3 to day 12. On 24h few α-SMA positiveinterititial cells and ED-1 positive macrophages were present. Fromday 3 the number of α-SMA positive interititial cells (myofibroblast)and ED-1 positive macrophages increased. Some tubular epithelialcells epressed α-SMA. The renal tubulointerstital expression ofTIMP-1was significantly associated with the relative volume ofinterititium and the postive area of α-SMA. Immunostainings forPCNA was evaluated from day 1 after UUO, there was a further increaseof PCNA-positive cell in tubulointerstitum at day 3, the peak ofproliferation. Conclusion: TIMP-1 was active in interititial andtubular cells in the early phase of fibrotic process and TIMP-1 mayhave an important role in mediat ing the tubulointerstital fibrosisafter UUO.