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 glomerulon ephritis, we hypothesized that podocyte injury is one of the important fact ors in bringing upon irreversible glomerular alterations. To verify this hy pothesis, we investigated whether podocyte injury induced by puromycin amin onucleoside (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 weigh t (BW) of puromycin aminonucleoside (PAN), and sacrificed at 7 days or 8 we eks after the mAb 1-22-3 injection. Results. Consecutive injections of 10 mg/100 g BW of PAN and mAb 1-22-3 cau sed the irreversible mesangial alteration with persistent proteinuria (at w eek 8, proteinuria 100.3 +/- 57.8 mg/24 h, matrix score 1.13 +/- 0.52, coll agen type I score 2.04 +/- 0.53, mRNA for collagen type 1227 +/- 79% to the group with a single injection of 1-22-3). Although single injection of 5 m g/100 g BW of PAN was not capable of inducing abnormal proteinuria, consecu tive injections of 5 mg/100 g BW of PAN and mAb 1-22-3 also caused irrevers ible mesangial alteration and persistent proteinuria. Conclusions. Podocyte injury might be an important factor that exacerbates mesangial proliferation and mesangial matrix expansion. The irreversible me sangial 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 progres sive mesangial alteration.