Changes in glomerular epithelial cells induced by FGF2 and FGF2 neutralizing antibody in puromycin aminonucleoside nephropathy.
In the present study, two series of experiments were done with PAN nephropathy rats given fibroblast growth factor 2 (FGF2) or FGF2 neutralizing antibodies. In the first series of experiments, a dose of 10 micrograms of FGF2 (FGF2 group), 40 micrograms of an FGF2 neutralizing antibody (Anti-FGF2 group) or an equal volume of physiological saline (Control group) was administered for four days after PAN injection. Urinary protein increased more in the FGF2 group than in the other two groups. PCNA (+) glomerular cells were found in decreasing order in groups FGF2, Control and Anti-FGF2. Most of the PCNA (+) cells were podocytes and epithelial cells of Bowman's capsule. Staining for desmin, a marker of podocyte injury, was significantly reduced in the Anti-FGF2 group. Glomerular adhesive lesions were found in decreasing order in groups FGF2, Control and Anti-FGF2. The second series of experiments was designed to study the effects of FGF2 neutralizing antibody (40 micrograms for 5 days after PAN injection, in MoAb group) on severely damaged podocytes caused by repeated (two courses) injections in the PAN nephropathy rats. The results were the same as those in series 1. An increase in urinary protein excretion was observed in both groups, but on the 40th day, the level of proteinuria in the MoAb group decreased abruptly. It was observed that the MoAb group had few adhesive glomeruli compared to the IgG group (administration of mouse IgG) and the PCNA (+) epithelial cells of Bowman's capsule were also few. It was supposed that FGF2 would promote the formation of adhesive lesions by stimulating the proliferation of podocytes and epithelial cells of Bowman's capsule. Additionally, FGF2 itself was thought to impair podocytes because of the increasing desmin score and proteinuria.
Sasaki
T
T
Department of Internal Medicine, Kawasaki Medical School, Okayama, Japan.
Jyo
Y
Y
Tanda
N
N
Kawakami
Y
Y
Nohno
T
T
Tamai
H
H
Osawa
G
G
D000818:Animals; D000900:Anti-Bacterial Agents / Q000009:adverse effects*; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D003893:Desmin / Q000032:analysis; D004848:Epithelium / Q000276:immunology; D016222:Fibroblast Growth Factor 2 / Q000276:immunology / Q000494:pharmacology*; D005921:Glomerulonephritis / Q000139:chemically induced* / Q000473:pathology; D007274:Injections, Intraperitoneal; D007678:Kidney Glomerulus / Q000737:chemistry / Q000166:cytology* / Q000276:immunology; D008297:Male; D009500:Neutralization Tests; D011507:Proteinuria / Q000139:chemically induced / Q000473:pathology; D011692:Puromycin Aminonucleoside / Q000009:adverse effects*; D051381:Rats; D017208:Rats, Wistar
D000900:Anti-Bacterial Agents; D000911:Antibodies, Monoclonal; D003893:Desmin; D016222:Fibroblast Growth Factor 2; D011692:Puromycin Aminonucleoside