RGD Reference Report - Glomerular hypertrophy precedes albuminuria and segmental loss of podoplanin in podocytes in Munich-Wistar-Fromter rats. - Rat Genome Database

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Glomerular hypertrophy precedes albuminuria and segmental loss of podoplanin in podocytes in Munich-Wistar-Fromter rats.

Authors: Ijpelaar, DH  Schulz, A  Koop, K  Schlesener, M  Bruijn, JA  Kerjaschki, D  Kreutz, R  De Heer, E 
Citation: Ijpelaar DH, etal., Am J Physiol Renal Physiol. 2008 Apr;294(4):F758-67. Epub 2008 Jan 16.
RGD ID: 2292240
Pubmed: PMID:18199599   (View Abstract at PubMed)
DOI: DOI:10.1152/ajprenal.00457.2007   (Journal Full-text)

Focal segmental glomerulosclerosis (FSGS) is a common cause of end-stage renal disease. Albuminuria is a risk factor for FSGS and is influenced by environmental, genetic, and sex-specific factors. Podocytes play a central role in the development of albuminuria, but the precise relationship between early glomerular and podocyte-associated damage and albuminuria is unclear. Furthermore, experimental findings demonstrate a sex difference in development of albuminuria and FSGS. We investigated the early glomerular changes in male Munich-Wistar-Fromter (MWF) rats, which spontaneously develop albuminuria, and male albuminuria-resistant spontaneously hypertensive rats (SHR). In addition, since female MWF rats are protected from overt proteinuria and progressive renal disease, we compared the phenotypic changes in podocytes during early development of albuminuria in male and female MWF rats. In male MWF rats, glomerular hypertrophy preceded the onset of albuminuria and was greater than in male SHR. Albuminuria developed starting at 6 wk of age and coincided with focal and segmental loss of podoplanin, increased expression of desmin, entrapment of albumin in affected podocytes, and focal and segmental foot process effacement at the ultrastructural level. Other podocyte-associated molecules, such as nephrin and zonula occludens 1, were unaffected. Early glomerular hypertrophy and podocyte damage did not differ between male and female MWF rats. Our data show for the first time that albuminuria in male and female MWF rats is preceded by glomerular hypertrophy and accompanied by focal and segmental loss of podoplanin when FSGS was not yet present.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Albuminuria  ISOPdpn (Rattus norvegicus)2292240; 2292240 RGD 
Albuminuria  IEP 2292240 RGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
albuminuria  IAGP 2292240compared to SHR/FubRkbRGD 
decreased urine albumin level sexual_dimorphism IAGP 2292240compared to male SHR/FubRkbRGD 

Objects Annotated

Genes (Rattus norvegicus)
Pdpn  (podoplanin)

Genes (Mus musculus)
Pdpn  (podoplanin)

Genes (Homo sapiens)
PDPN  (podoplanin)

Strains
MWF/FubRkb  (Munich Wistar Fromter)


Additional Information