[Diabetic nephropathy and plasminogen activator inhibitor 1 in urine samples].
Plasminogen activator inhibitor-1 (PAI-1) may contribute to renal fibrosis because of its involvement in matrix (ECM) accumulation through inhibition of plasmin-dependent ECM degradation. The aim of this study is to determine urinary PAI-1 concentrations and its intrarenal localization in patients with various renal diseases and to identify inducers for PAI-1 expression in human cultured proximal renal tubular cells (HRCs). Urinary PAI-1 concentrations were significantly higher in patients with overt diabetic nephropathy (DN, n=36) than in proliferative glomerulonephritis (PGN, n=8), nephrotic syndrome (NS, n=10) and healthy controls (n=12). Urinary PAI-1 concentrations (ng/gCr) were directly correlated with urinary N-acetyl glucosaminidase (NAG) levels (r=0.58, p<0.05). As for intrarenal localization of PAI-1 antigen, strong stainings for PAI-1 were observed in proximal tubular cells of renal biopsy samples from patients with DN, while no stainings for PAI-1 were found in renal tissues of PGN or NS. Immunoblot analysis revealed the presence of PAI-1 protein in whole cell lyzates from HRCs grown to semiconfluency. Exposure of growth-arrested HRCs with hypoxia (1% O2) or TNF-alpha (10 ng/ml) for 24 hours increased the secretion rate of PAI-1 protein by about 2.0-fold, while 24-hour treatment with high glucose (450 mg/dl) did not increase PAI-1 secretion at all, compared with that of the control cells under normal glucose (100 mg/dl) and normoxia (18% O2). These findings suggest that PAI-1 expression is upregulated especially in the proximal renal tubular cells of DN, which may be explained partially by hypoxia and inflammatory cytokines but not high glucose.
Torii
Kunio
K
Department of Clinical Laboratory Medicine, University of Fukui, Yoshida-gun.
Kimura
Hideki
H
Li
Xuan
X
Okada
Toshiharu
T
Imura
Toshio
T
Oida
Koji
K
Miyamori
Isamu
I
Furusaki
Fumio
F
Ono
Tomoko
T
Yoshida
Haruyoshi
H
D003928:Diabetic Nephropathies / Q000652:urine*; D005921:Glomerulonephritis / Q000652:urine; D006801:Humans; D009404:Nephrotic Syndrome / Q000652:urine; D017395:Plasminogen Activator Inhibitor 1 / Q000652:urine*
D017395:Plasminogen Activator Inhibitor 1