[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.
Department of Clinical Laboratory Medicine, University of Fukui, Yoshida-gun.
Kunio
K
Torii
Hideki
H
Kimura
Xuan
X
Li
Toshiharu
T
Okada
Toshio
T
Imura
Koji
K
Oida
Isamu
I
Miyamori
Fumio
F
Furusaki
Tomoko
T
Ono
Haruyoshi
H
Yoshida
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