Cheng Hui, Chen Cheng, Wang Siyuan
Division of Nephrology, Wuhan University, Renmin Hospital , Wuhan , People's Republic of China.
Ren Fail. 2014 Sep;36(8):1322-7. doi: 10.3109/0886022X.2014.934694. Epub 2014 Jul 10.
To investigate the effect of urokinase-type plasminogen activator (uPA) on mesangial matrix in the kidney of diabetic rats and its related mechanisms.
Diabetic Sprague-Dawley (SD) rats induced by intraperitoneal injection of streptozotocin (STZ) were randomly and evenly divided into two groups: DM + vehicle, and DM + uPA (2500 U kg(-1) uPA via tail vein once a day for four weeks). The normal SD rats without diabetes were considered as control group. Rats in the three groups were executed and the heart blood was sampled for determination of blood glucose and serum creatinine. Meanwhile, kidney tissues of rats were also harvest for measurement of glomerular area, volume, and mesangial area by periodic acid silver methenamine (PASA) staining. The expression of urokinase-type plasminogen activator receptor (uPAR), plasminogen activator inhibitor-1 (PAI-1), and collagen IV in renal tissues was tested with immunohistochemistry.
Compared with control, the DM rats had obvious albuminuria, significantly (p < 0.01) increased glomerular volume and mesangial matrix area, and significantly (p < 0.05) higher expression of uPAR, PAI-1 and collagen IV in mesangial matrix, significantly up-regulated (p < 0.05) glomerular uPAR, PAI-1, and collagen IV expression. After treated with uPA, the diabetic rats had significantly (p < 0.05) reduced albuminuria, significantly (p < 0.01) improved glomerular volume and mesangial matrix, significantly (p < 0.05) down-regulated PAI-1 and collagen IV expression in mesangial matrix. However, the uPAR expression in renal tissues were unchangeable (p > 0.05) and PAI-1 and collagen IV expression were significantly (p < 0.05) reduced when diabetic rats were treated with uPA.
uPA can down-regulate glomerular PAI-1 expression in the DM rats but not significantly influence uPAR expression, suggesting that uPA might regulate the mesangial cell (MC) and its matrix expression and improve diseased diabetic mesangial matrix via its combination with uPAR to uptake PAI-1 and accelerate its degradation.
探讨尿激酶型纤溶酶原激活剂（uPA）对糖尿病大鼠肾脏系膜基质的影响及其相关机制。
将腹腔注射链脲佐菌素（STZ）诱导的糖尿病斯普拉格-道利（SD）大鼠随机均分为两组：糖尿病+溶剂组和糖尿病+uPA组（通过尾静脉每天注射1次2500 U/kg uPA，共4周）。将未患糖尿病的正常SD大鼠作为对照组。处死三组大鼠，采集心脏血液测定血糖和血清肌酐。同时，也采集大鼠肾脏组织，通过高碘酸银甲胺（PASA）染色测量肾小球面积、体积和系膜面积。用免疫组织化学法检测肾组织中尿激酶型纤溶酶原激活剂受体（uPAR）、纤溶酶原激活物抑制剂-1（PAI-1）和IV型胶原的表达。
与对照组相比，糖尿病大鼠有明显蛋白尿，肾小球体积和系膜基质面积显著增加（p<0.01），系膜基质中uPAR、PAI-1和IV型胶原的表达显著升高（p<0.05），肾小球uPAR、PAI-1和IV型胶原表达显著上调（p<0.05）。用uPA治疗后，糖尿病大鼠蛋白尿显著减少（p<0.05），肾小球体积和系膜基质显著改善（p<0.01），系膜基质中PAI-1和IV型胶原表达显著下调（p<0.05）。然而，糖尿病大鼠用uPA治疗后，肾组织中uPAR表达无变化（p>0.05），PAI-1和IV型胶原表达显著降低（p<0.05）。
uPA可下调糖尿病大鼠肾小球PAI-1表达，但对uPAR表达无显著影响，提示uPA可能通过与uPAR结合摄取PAI-1并加速其降解来调节系膜细胞（MC）及其基质表达，改善糖尿病系膜病变基质。
