Correlation between thrombospondin-1 mediated thrombofibrinolysis and tubulointerstitial fibrosis in remnant renal tissues of 5/6 nephrectomized young rats

Objective To investigate how thrombospondin-1 (TSP-1) expression affects and correlates to the thrombofibrinolysis during progression of chronic renal lesions or tubulointerstitial fibrosis in remnant renal tissues of 5/6 nephrectomy young rats, and to study the efficacy of intervention with angiotensin converting enzyme inhibitor (ACEI). Methods Five sixths nephrectomized (5/6 NX) young rats were used as a classical chronic renal failure model. The rats were randomized into the untreated NX group, ACEI-treated NX group or sham group. At the start of this experiment and at weeks 4, 8 and 12, body weight, blood pressure and 24 h proteinuria of the rats were measured protein expressions of TSP-1, PAI-1, TGF-β1, uPA and tPA in remnant renal tissues were determined using immunohisto-chemical techniques. Changes in these values and interactions among them were evaluated. Effects of ACEI intervention were also assessed. Results Immunohistochemical staining of the renal tissue showed lowered expressions of tPA and uPA and increased expression of PAI-1 in untreated NX rats vs sham-operated rats. All NX rats showed simultaneous up-regulation of TSP-1 and TGF-β1 in remnant renal tissues as compared with sham-operated ones. Among rats treated with ACEI, the expression of TSP-1 and TGF-β1 appeared to be down-regulated. Positive correlation was identified between TSP-1 expression and tendency of glomerulosclerosis or tubulointerstitial fibrosis. Moreover, the expression of TSP-1 was positively correlated with that of TGF-β1 or PAI-1, and negatively correlated with that of uPA or tPA. Conclusion TSP-1 and TGF-β1 were demonstrated to be major promoters for tubulointerstitial fibrosis. Over-expression of TSP-1 may lead to disordered expressions of tPA, uPA and PAI-1 in renal tissues, which can result in imbalance of thrombofibrinolytic system and progression of renal lesions