STUDIES ON THE MECHANISMS OF PROTEINURIA AND PROGRESSION OF THE GLOMERULOPATHY OF OM/N RATS.

1994 Fiscal Year Final Research Report Summary

• Project/Area Number: 06660415
• Research Category: Grant-in-Aid for General Scientific Research (C)
• Allocation Type: Single-year Grants
• Research Field: Applied veterinary science
• Research Institution: Azabu University
• Principal Investigator: SHIROTA Kinji AZABU UNIVERSITY,SCHOOL OF VETERINARY MEDICINE,ASSOCIATE PROFESSOR, 獣医学部, 助教授 (70147974)
• Co-Investigator(Kenkyū-buntansha): FUJISE Hiroshi AZABU UNIVERSITY,SCHOOL OF VETERINARY MEDICINE,PROFESSOR, 獣医学部, 教授 (40106232)
• Project Period (FY): 1994 – 1995
• Keywords: PROTEINURIA / NEPHROTIC SYNDROME / GLOMERULOSCLEROSIS / CHRONIC RENAL FAILURE / RAT

Research Abstract

Pathological and biochemical examinations were carried out on the kidneys and urine of Osborne-Mendel/NIH (Om/N) rats showing nephrotic syndrome-like nephropathy.
The results of this study are listed as follows. 1. Male Om/N rats showed selective proteinuria at an early of age, and soon after developed non-selective proteinuria. 2. Light microscopic changes in the glomeruli of Om/N rats were characterized by progressive degeneration and denudation of podocytes followed by local adhesion and segmental selerosis of the glomerular tufts. 3. No decrease in heparan sulfate in the glomerular tufts was detected by immunohistochemistry. 4. The number of anionic sites (ASs) in the glomerular basement membrane (GBM) was significantly less in Om/N rats than that in Sprague-Dawley rats without proteinuria. Also, the decrease in ASs of GBM in Om/N rats was dependent on the age of the rats. Unusual distribution of ASs in GBM and loss or decrease in ASs on the surface of podocytes were observed in the glomeruli of Om/N rats. 5. Isoelectric focusing electrophoresis indicated that the urine of Om/N rats included protein with lower isoelectric point as compared to that of F344 rats.
These results indicate that proteinuria might be induced by disturbance of the glomerular polyanion and the lesions of podocytes may be significant for the progression of glomerular lesions in Om/N rats. Molecular analyzes must be performed on heparan sulfate, podocaryxin type IV collagen and integrins of podocytes to clarify the mechanism for abnormalities in glomerular polyanion and progression of glomerular disease of Om/N rats.