RGD Reference Report - Pathophysiologic implications of reduced podocyte number in a rat model of progressive glomerular injury. - Rat Genome Database

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Pathophysiologic implications of reduced podocyte number in a rat model of progressive glomerular injury.

Authors: Macconi, Daniela  Bonomelli, Maria  Benigni, Ariela  Plati, Tiziana  Sangalli, Fabio  Longaretti, Lorena  Conti, Sara  Kawachi, Hiroshi  Hill, Prue  Remuzzi, Giuseppe  Remuzzi, Andrea 
Citation: Macconi D, etal., Am J Pathol. 2006 Jan;168(1):42-54. doi: 10.2353/ajpath.2006.050398.
RGD ID: 14401564
Pubmed: PMID:16400008   (View Abstract at PubMed)
PMCID: PMC1592676   (View Article at PubMed Central)
DOI: DOI:10.2353/ajpath.2006.050398   (Journal Full-text)

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.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
MWF/ZtmRatglomerulosclerosis  IAGP compared to Wi and 10-20 week MWFRGD 
MWF/ZtmRathypertension  IAGP compared to Wi nd 10 week MWFRGD 
MWF/ZtmRatproteinuria  IAGP compared to Wi and 10-20 week MWFRGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
MWF/ZtmRatdecreased podocyte number  IAGP compared to Wi and 10-20 week MWFRGD 
MWF/ZtmRatrenal glomerulus hypertrophy  IAGP compared to Wi and 10-20 week MWFRGD 

Objects Annotated

Strains
MWF/Ztm  (Munich Wistar Fromter)


Additional Information