切应力作用下肾近端小管上皮细胞纤溶酶原激活物(tPA和uPA)表达的变化及意义

Effects of Shear Stress on Expression of Plasminogen Activator(tPA and uPA) in Cultured Kidney Proximal Tubular Epithelial Cells and Its Significance

检测切应力作用下肾近端小管上皮细胞纤溶酶原激活物tPA和uPA mRNA表达的变化,探讨糖尿病肾病早期小管间质细胞外基质重塑的可能机制。用5 dyn/cm2和10 dyn/cm2的切应力处理肾近端小管上皮细胞(NRK-52E),作用时间分别为1、3和6 h,用RT-PCR法检测tPA及uPA mRNA的表达。结果表明:切应力呈大小和时间依赖性下调肾小管上皮细胞tPA及uPA mRNA的表达。在糖尿病肾病早期,高滤过引起的切应力增加可抑制肾近端小管上皮细胞tPA和uPA mRNA表达,导致肾小管间质纤维蛋白溶解活性降低,参与小管间质细胞外基质的重塑。

In this study, we assessed the effects of shear stress on the expression of plasminogen activator（tPA and uPA） mRNA in cultured NRK-52E cells （a kidney proximal tubular epithelial cell line of normal rat origin） and investigated the mechanism of tubulointerstitial extracellular matrix （ECM） remodeling in the early stage of diabetic nephropathy （DN）. The cultured NRK-52E cells were exposed to shear stress of 5 and 10 dyn/cm2 for 1, 3 and 6 hours respectively. Semi-quantity RT-PCR was used to detect the expression of tPA and uPA mRNA. Shear stress down-regulated the ex- pression of tPA and uPA mRNA in cultured NRK-52E cells in a maguimde and time-dependent way. The results suggested that the increased tubular shear stress in the early-stage of DN could decrease the expression of tPA and uPA in renal proximal tubular cells, lead to the reduction of tubulointerstitial fibrinolytic activity and involve in the remodeling of ECM.