Regulation of tissue plasminogen activator production in cultured human fetal mesangial cells.
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.
Yoshiko
B
B
Second Department of Internal Medicine, Hirosaki University School of Medicine, Hirosaki, Japan.
Yamabe
H
H
Osawa
H
H
Okumura
K
K
D002478:Cells, Cultured; D005333:Fetus / Q000166:cytology / Q000378:metabolism*; D005920:Glomerular Mesangium / Q000166:cytology / Q000187:drug effects / Q000196:embryology* / Q000378:metabolism; D006801:Humans; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis; D013917:Thrombin / Q000494:pharmacology; D010959:Tissue Plasminogen Activator / Q000096:biosynthesis*; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D017395:Plasminogen Activator Inhibitor 1; D016212:Transforming Growth Factor beta; D013917:Thrombin; D010959:Tissue Plasminogen Activator