Cellular localization of type 1 plasminogen activator inhibitor messenger RNA and protein in murine renal tissue.
Type 1 plasminogen activator inhibitor (PAI-1) may be markedly increased in the plasma of patients with endotoxemia and/or renal disease. To investigate renal PAI-1 production during acute endotoxemia, a murine model system was used. Mice were injected with either saline alone or saline containing 50 micrograms endotoxin, and sacrificed 3 hours later and their tissues analyzed for PAI-1 messenger RNA (mRNA) and antigen. Northern blot analysis confirmed that the level of renal PAI-1 mRNA was greatly increased in the endotoxemic mice relative to the saline controls. In situ hybridization was then performed to determine the cellular localization of PAI-1 mRNA within the renal tissues. In the control kidneys, low levels of PAI-1 mRNA were detected in the renal papilla and in the muscular walls of renal arteries. However, in the endotoxemic mice, an intense hybridization signal for PAI-1 mRNA was observed in glomerular and peritubular cells. These cells also stained positively for von Willebrand factor antigen, an endothelial cell-specific marker. The PAI-1 mRNA hybridization signal could further be observed in peritubular endothelial cells in the medulla and in endothelial cells of veins and arteries throughout the kidney. Immunochemical analysis revealed that PAI-1 antigen co-localized to the cytoplasm of cells expressing PAI-1 mRNA. This study provides the first direct evidence that PAI-1 is induced in endothelial cells of the kidney during endotoxemia in vivo and suggests a role for PAI-1 in the pathogenesis of renal disease.
Keeton
M
M
Committee on Vascular Biology, Scripps Research Institute, La Jolla, CA 92037.
Eguchi
Y
Y
Sawdey
M
M
Ahn
C
C
Loskutoff
D J
DJ
D000273:Adipose Tissue / Q000737:chemistry / Q000166:cytology; D000818:Animals; D015152:Blotting, Northern; D007519:Isoantigens / Q000032:analysis; D007668:Kidney / Q000098:blood supply / Q000737:chemistry* / Q000166:cytology; D007672:Kidney Cortex / Q000737:chemistry / Q000166:cytology; D007678:Kidney Glomerulus / Q000737:chemistry / Q000648:ultrastructure; D007679:Kidney Medulla / Q000737:chemistry / Q000166:cytology; D051379:Mice; D016253:Microscopy, Immunoelectron; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis* / Q000235:genetics* / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis* / Q000235:genetics
D007519:Isoantigens; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger