Effects of urokinase on renal interstitial fibrosis and transforming growth factor-beta1 in the kidney of rats with chronic cyclosporine A nephropathy / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effects of urokinase on renal interstitial fibrosis and transforming growth factor-beta1 (TGF-beta1) in the kidney of rats with chronic cyclosporine A nephropathy.</p><p><b>METHODS</b>Male Sprague-Dawley rats on low-salt diet were randomly divided into control (VH), CsA-treated (CsA), CsA+2000 U/kg.day uPA (CsA+U2) and CsA+6000 U.kg.3 days (CsA+U6) groups. The rats were given CsA intragastrically for 4 weeks to prepare CsA-induced chronic nephropathy model. Masson staining was used to examine fibrin deposition. Western blotting and reversal transcription polymerase chain reaction were employed to evaluate urokinase-type plasminogen activator (uPA) and TGF-beta1 protein and gene expressions, respectively.</p><p><b>RESULTS</b>CsA can increase fibrin deposition and the expression of TGF-beta1 in the renal tissue, which were significantly reduced after uPA treatment (P<0.05).</p><p><b>CONCLUSION</b>Continuous low-dose uPA treatment can reduce renal interstitial fibrosis in rats possibly in association with its inhibitory effect on TGF-beta1 expression.</p>

Role of integrin-linked kinase in renal tubular epithelial-mesenchymal transition and the regulatory effect of urokinase on its expression in mice with obstructive nephropathy / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the role of integrin-linked kinase (ILK) on renal tubular epithelial-mesenchymal transition and the regulatory effect of urokinase on LIK expression in mice with obstructive nephropathy.</p><p><b>METHODS</b>Normal male mice were randomly divided into sham-operated group (n=20), unilateral ureteral obstruction (UUO) group (n=28), and UUO with urokinase treatment group (uPA, n=28), and UUO was induced surgically in the latter two groups. The mice were sacrificed on days l, 3, 7 and 14 after the surgery, and renal interstitial fibrosis (RIF) was graded according to the result of Masson staining. The expression of ILK in the renal tissues of the rats was examined by immunofluorescence staining and Western blotting, and the expression of E-cadherin was detected by immunohistochemistry. RT-PCR was used to examine the mRNA expressions of ILK, E-cadherin and alpha-smooth muscle actin (alpha-SMA).</p><p><b>RESULTS</b>The expressions of ILK mRNA and protein were significantly increased in UUO group, but significantly decreased by treatment with uPA (P<0.05). The expression of alpha-SMA mRNA level was significantly increased, while E-cadherin decreased in mice with UUO on day 3 after the surgery. Treatment with uPA significantly inhibited such effects (P<0.05).</p><p><b>CONCLUSION</b>ILK plays an important role in renal interstitial fibrosis by mediating epithelial-mesenchymal transition. Urokinase attenuates renal tubulointerstitial fibrosis in mice with UUO possibly by inhibiting ILK expression and preventing tubular epithelial-mesenchymal transition.</p>

Effect of urokinase on renal interstitial inflammation in rats with chronic cyclosporine A nephropathy and its possible mechanism / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the protective effect of urokinase on renal interstitial inflammation and fibrosis in rats with chronic cyclosporine A (CsA)-induced nephropathy.</p><p><b>METHODS</b>Male SD rats were fed on low salt diet (0.05% sodium) for 7 days and randomized into 4 groups for treatment with CsA, CsA+continuous low-dose uPA (U2), intermittent CsA+ high-dose uPA (U6) or vehicle (control group). In the former 3 groups, the rats were subjected to daily intragastric administration of CsA (25 mg/kg) for 4 weeks to establish CsA-induced chronic nephropathy model, and those in U2 and U6 groups were given uPA at 2000 U/kg daily or at 6000 U/kg every 3 days, respectively. Four weeks after the treatment, the renal function and 24-h proteinuria were assessed, and Masson staining was used for examining fibrin deposition. Semi-quantitative immunohistochemical staining was employed for evaluation of ED-1-positive cells, urokinase-type plasminogen activator (uPA) and transforming growth factor-beta1 (TGF-beta 1).</p><p><b>RESULTS</b>Four weeks after the treatment, the CsA-treated rats showed significantly elevated serum creatinine (Scr), blood urea nitrogen (BUN) and increased urine proteins. Continuous administration of low-dose uPA resulted in significantly reduced Scr, BUN and 24-h urine protein excretion, while intermittent high-dose uPA treatment did not produce such changes. CsA increased fibrin deposition, total number of macrophages in renal interstitium and TGF-beta1 expression in the renal tissue, which were significantly reduced in U2 group (P<0.05) but not in U6 group (P>0.05).</p><p><b>CONCLUSION</b>Continuous administration of low-dose uPA may reduce interstitial fibrin deposition and alleviate renal interstitial inflammation in rats with chronic CsA nephropathy, possibly by reducing the number of macrophages and TGF-beta1 expression in the renal tissue.</p>