Yoshiko B, Yamabe H, Osawa H, Okumura K
Second Department of Internal Medicine, Hirosaki University School of Medicine, Hirosaki, Japan.
Exp Nephrol. 1998 Nov-Dec;6(6):508-13. doi: 10.1159/000020565.
Glomerular fibrin deposition is thought to be one of the factors causing progressive glomerular injury and may be related to defective intraglomerular fibrinolysis. Recently, it was shown that tissue plasminogen activator (t-PA) is produced by mesangial cells and is associated with degradation of the extracellular matrix. This study was designed to clarify the factors regulating t-PA production in human mesangial cells. The levels of t-PA activity, t-PA antigen and t-PA inhibitor-1 (PAI-1) antigen were estimated in the supernatants of cultured human fetal mesangial cells incubated for 72 h with thrombin, IL-Ibeta, IL-6, IL-10, and transforming growth factor-beta (TGF-beta). The t-PA activity was measured by an amidolytic assay, and the levels of t-PA antigen and PAI-1 antigen were also measured by enzyme-linked immunosorbent assay. Thrombin increased t-PA activity and TGF-beta decreased it in parallel with t-PA antigen level, although these agents did not affect the synthesis of PAI-1. Incubation with IL-1beta, IL-6 and IL-10 did not change the t-PA activity. It was concluded that the release of t-PA from human fetal mesangial cells was stimulated by thrombin and inhibited by TGF-beta in parallel with that of t-PA antigen. These factors may participate in the glomerular fibrin deposition and the accumulation of extracellular matrix.
肾小球纤维蛋白沉积被认为是导致进行性肾小球损伤的因素之一，可能与肾小球内纤维蛋白溶解缺陷有关。最近的研究表明，组织纤溶酶原激活物（t-PA）由系膜细胞产生，并与细胞外基质的降解有关。本研究旨在阐明调节人系膜细胞中t-PA产生的因素。在用凝血酶、白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）、白细胞介素-10（IL-10）和转化生长因子-β（TGF-β）孵育72小时的人胎儿系膜细胞培养上清液中，评估了t-PA活性、t-PA抗原和t-PA抑制剂-1（PAI-1）抗原的水平。通过酰胺水解测定法测量t-PA活性，也通过酶联免疫吸附测定法测量t-PA抗原和PAI-1抗原的水平。凝血酶增加了t-PA活性，TGF-β则降低了t-PA活性，且与t-PA抗原水平平行，尽管这些试剂不影响PAI-1的合成。用IL-1β、IL-6和IL-10孵育并未改变t-PA活性。得出的结论是，凝血酶刺激人胎儿系膜细胞释放t-PA，而TGF-β则抑制t-PA释放，且与t-PA抗原的释放平行。这些因素可能参与肾小球纤维蛋白沉积和细胞外基质的积累。
