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Pathophysiologic Implications of Reduced Podocyte Number in a Rat Model of Progressive Glomerular Injury
- Publication Year :
- 2006
- Publisher :
- American Society for Investigative Pathology, 2006.
-
Abstract
- Changes in podocyte number or density have been suggested to play an important role in renal disease progression. Here, we investigated the temporal relationship between glomerular podocyte number and development of proteinuria and glomerulosclerosis in the male Munich Wistar Fromter (MWF) rat. We also assessed whether changes in podocyte number affect podocyte function and focused specifically on the slit diaphragm-associated protein nephrin. Age-matched Wistar rats were used as controls. Estimation of podocyte number per glomerulus was determined by digital morphometry of WT1-positive cells. MWF rats developed moderate hypertension, massive proteinuria, and glomerulosclerosis with age. Glomerular hypertrophy was already observed at 10 weeks of age and progressively increased thereafter. By contrast, mean podocyte number per glomerulus was lower than normal in young animals and further decreased with time. As a consequence, the capillary tuft volume per podocyte was more than threefold increased in older rats. Electron microscopy showed important changes in podocyte structure of MWF rats, with expansion of podocyte bodies surrounding glomerular filtration membrane. Glomerular nephrin expression was markedly altered in MWF rats and inversely correlated with both podocyte loss and proteinuria. Our findings suggest that reduction in podocyte number is an important determinant of podocyte dysfunction and progressive impairment of the glomerular permselectivity that lead to the development of massive proteinuria and ultimately to renal scarring.
- Subjects :
- Male
Pathology
medicine.medical_specialty
Blotting, Western
Renal function
urologic and male genital diseases
Article
Pathology and Forensic Medicine
Podocyte
Nephropathy
Nephrin
Microscopy, Electron, Transmission
medicine
Animals
RNA, Messenger
Rats, Wistar
Proteinuria
biology
urogenital system
Glomerulosclerosis, Focal Segmental
Podocytes
Reverse Transcriptase Polymerase Chain Reaction
Glomerulosclerosis
Membrane Proteins
Glomerular Hypertrophy
medicine.disease
Immunohistochemistry
female genital diseases and pregnancy complications
Rats
Disease Models, Animal
medicine.anatomical_structure
Hypertension
biology.protein
Slit diaphragm
Microscopy, Electron, Scanning
medicine.symptom
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....e2f4072a616decb5a8fafa51e3c35989