Podocyte injuries exacerbate mesangial proliferative glomerulonephritis.
BACKGROUND
From the observations of morphology seen in early phases of the experimental models of the irreversible mesangial proliferative glomerulonephritis, we hypothesized that podocyte injury is one of the important factors in bringing upon irreversible glomerular alterations. To verify this hypothesis, we investigated whether podocyte injury induced by puromycin aminonucleoside (PAN) injection affects the mesangial alterations of anti-Thy 1.1 glomerulonephritis.


METHODS
Female Wistar rats were injected with 0.5 mg monoclonal antibody (mAb) 1-22-3 five days after the injection of 10 mg or 5 mg/100 g body weight (BW) of puromycin aminonucleoside (PAN), and sacrificed at 7 days or 8 weeks after the mAb 1-22-3 injection.


RESULTS
Consecutive injections of 10 mg/100 g BW of PAN and mAb 1-22-3 caused the irreversible mesangial alteration with persistent proteinuria (at week 8, proteinuria 100.3 +/- 57.8 mg/24 h, matrix score 1.13 +/- 0.52, collagen type I score 2.04 +/- 0.53, mRNA for collagen type I 227 +/- 79% to the group with a single injection of 1-22-3). Although single injection of 5 mg/100 g BW of PAN was not capable of inducing abnormal proteinuria, consecutive injections of 5 mg/100 g BW of PAN and mAb 1-22-3 also caused irreversible mesangial alteration and persistent proteinuria.


CONCLUSIONS
Podocyte injury might be an important factor that exacerbates mesangial proliferation and mesangial matrix expansion. The irreversible mesangial alterations caused by consecutive injections of PAN and mAb 1-22-3 may be a novel model that could be used to analyze the mechanism of progressive mesangial alteration.
Morioka
Y
Y
Department of Cell Biology, Institute of Nephrology, Faculty of Medicine, Niigata University, Japan.
Koike
H
H
Ikezumi
Y
Y
Ito
Y
Y
Oyanagi
A
A
Gejyo
F
F
Shimizu
F
F
Kawachi
H
H
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D005260:Female; D005920:Glomerular Mesangium / Q000187:drug effects / Q000473:pathology*; D015432:Glomerulonephritis, Membranoproliferative / Q000139:chemically induced / Q000473:pathology*; D007668:Kidney / Q000473:pathology*; D011692:Puromycin Aminonucleoside / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018800:Thy-1 Antigens / Q000276:immunology; D013997:Time Factors
D000911:Antibodies, Monoclonal; D018800:Thy-1 Antigens; D011692:Puromycin Aminonucleoside