Role of TIMP-1 expression in renal tubulointerstital lesion induced by unilateral ureteral obstruction

Objective To explore the role of tissue inhibitor of metalloproteinase-1 (TIMP-1 )in the renal tubulointerstitial lesions induced by unilateral ureteral obstruction (UUO) . Methods Rats were sacrificed at 1, 3, 5, 7 and 14 days after UUO or sham-surgery. The protein expression of TIMP-1 ,α-smooth muscle actin(α-SMA) .proliferating cell nucleus antigen (PCNA) and ED-1 in tubulointerstitium were detected by immunohistochemistry at each time point. Rusults TIMP-1 expression in renal tubulointerstitium increased progressively starting from 24 hours to day 14 post-ligation. TIMP-1 was mainly expressed in interstitial and some tubular cells. On 24 hours post-ligation a few α-SMA-positive interstitial cells and ED-1-positive macrophages were present. From day 3 the number of a-SMA-positive interstitial cells and ED-1-positive macrophages increased. Some tubular epithelial cells also expressed α-SMA. The renal tubulointersital expression of TIMP-1 was significantly associated with the relative volume of interstitium and the postive area of α-SMA. The expression of PCNA in tubular cells peaked at day 3 after UUO, then decreased, but there were still many PCNA-positive interstitial cells at day 7 and day 14. Conclusion TIMP-1 is active in interstitial and tubular cells in the early phase of fibrotic process and may play an important role in mediating the tubulointerstital lesions after UUO.