Effect of endothelin 1 on fibrinolysis and plasminogen activator inhibitor 1 synthesis in rat mesangial cells.
Endothelins (ETs) have been known to have a variety of biological functions such as mitogenic stimulation, natriuresis and the stimulation of the proteolytic activity in addition to vasoconstrictive action, which may participate in the process of glomerular diseases pathophysiologically. In this study, the effects of ET-1 on fibrinolysis, plasminogen activator inhibitor 1 (PAI-1) synthesis and PAI-1 mRNA expression were examined in cultured rat mesangial cells (MCs). The addition of ET-1 (10(-11) to 10(-7) M) into MC cultures reduced fibrinolytic activities assayed by fibrin autography in a dose-dependent manner. For the assay of PAI-1 synthesis, MC culture media metabolically labeled with 35S-methionine were analyzed by SDS-PAGE with fluorography and immuno-precipitation using rabbit antirat PAI-1 antibody. Exposure to ET-1 for 24 h produced a clear dose-dependent effect on the PAI-1 release from the MCs. PAI-1 mRNA expression was also enhanced in parallel with the concentration of ET-1 in the conditioned media. These findings indicate that ET-1 participates in fibrinolysis and the PAI-1 synthesis by MCs, which may thus regulate the degradation of the extracellular matrix in the glomerular microenvironment.
Iwamoto
T
T
Second Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Tamaki
K
K
Nakayama
M
M
Okuda
S
S
Fujishima
M
M
D000818:Animals; D001345:Autoradiography; D015152:Blotting, Northern; D002478:Cells, Cultured; D004591:Electrophoresis, Polyacrylamide Gel; D019332:Endothelin-1 / Q000494:pharmacology*; D005337:Fibrin / Q000378:metabolism; D005342:Fibrinolysis / Q000187:drug effects*; D005920:Glomerular Mesangium / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008715:Methionine / Q000378:metabolism; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis*; D011233:Precipitin Tests; D012333:RNA, Messenger / Q000096:biosynthesis; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D013268:Stimulation, Chemical
D019332:Endothelin-1; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D005337:Fibrin; D008715:Methionine