title: Effect of angiotensin II on plasminogen activator inhibitor-1 production by cultured human mesangial cells.
abstract: Angiotensin II is a vasoactive peptide that has been widely implicated in the pathogenesis of glomerular disease. Some of its effects are thought to be independent of changes in blood pressure. Plasmin is a key regulator of fibrinolysis and extracellular matrix turnover. The conversion of plasminogen to plasmin by plasminogen activators (PAs) is controlled by their specific inhibitor, PAI-1. In this study we report the effects of angiotensin II on the production of PA inhibitor-1 (PAI-1) and tissue-type PA (t-PA) by glomerular mesangial cells in culture. Angiotensin II significantly increased the production of PAI-1 in the supernatant of mesangial cells (p < 0.05) in a dose-dependent manner, the maximum stimulation occurring at a concentration of 10(-5) M. The effect was not mediated by transforming growth factor-beta (TGF-beta), which is known to be induced by angiotensin II; TGF-beta itself can increase PAI-1 expression. Angiotensin II did not alter t-PA production or incorporation of matrix fibronectin but did increase cellular proliferation and 3H-thymidine uptake. The increase in PAI-1 by angiotensin II may contribute to the persistence of fibrin deposits and extracellular matrix accumulation, providing another mechanism whereby angiotensin II contributes to glomerular dysfunction.
authors.affiliation: Department of Molecular and Cell Biology, University of Aberdeen, UK. h.m.wilson@abdn.ac.uk
authors.forename: H M
authors.initials: HM
authors.lastname: Wilson
authors.forename: N E
authors.initials: NE
authors.lastname: Haites
authors.forename: N A
authors.initials: NA
authors.lastname: Booth
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D015152:Blotting, Northern; D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured; D005337:Fibrin / Q000378:metabolism; D005353:Fibronectins / Q000096:biosynthesis; D005920:Glomerular Mesangium / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis*; D013268:Stimulation, Chemical; D010959:Tissue Plasminogen Activator / Q000096:biosynthesis
chemical_list: D005353:Fibronectins; D017395:Plasminogen Activator Inhibitor 1; D000804:Angiotensin II; D005337:Fibrin; D010959:Tissue Plasminogen Activator