title: Albuminuria is associated with too few glomeruli and too much testosterone.
abstract: Normally, the glomerular filtration barrier almost completely excludes circulating albumin from entering the urine. Genetic variation and both pre- and postnatal environmental factors may affect albuminuria in humans. Here we determine whether glomerular gene expression in mouse strains with naturally occurring variations in albuminuria would allow identification of proteins deregulated in relatively 'leaky' glomeruli. Albuminuria increased in female B6 to male B6 to female FVB/N to male FVB/N mice, whereas the number of glomeruli/kidney was the exact opposite. Testosterone administration led to increased albuminuria in female B6 but not female FVB/N mice. A common set of 39 genes, many expressed in podocytes, were significantly differentially expressed in each of the four comparisons: male versus female B6 mice, male versus female FVB/N mice, male FVB/N versus male B6 mice, and female FVB/N versus female B6 mice. The transcripts encoded proteins involved in oxidation/reduction reactions, ion transport, and enzymes involved in detoxification. These proteins may represent novel biomarkers and even therapeutic targets for early kidney and cardiovascular disease.
authors: Nephro-Urology Unit, UCL Institute of Child Health, London, UK. d.long@ucl.ac.uk
authors: David A
authors: DA
authors: Long
authors: Maria
authors: M
authors: Kolatsi-Joannou
authors: Karen L
authors: KL
authors: Price
authors: Cecile
authors: C
authors: Dessapt-Baradez
authors: Jennifer L
authors: JL
authors: Huang
authors: Eugenia
authors: E
authors: Papakrivopoulou
authors: Mike
authors: M
authors: Hubank
authors: Ron
authors: R
authors: Korstanje
authors: Luigi
authors: L
authors: Gnudi
authors: Adrian S
authors: AS
authors: Woolf
mesh_terms: D000419:Albuminuria / Q000209:etiology* / Q000235:genetics / Q000473:pathology / Q000652:urine; D000818:Animals; D001794:Blood Pressure; D002478:Cells, Cultured; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D005838:Genotype; D060730:Glomerular Filtration Barrier / Q000378:metabolism; D007678:Kidney Glomerulus / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010539:Permeability; D010641:Phenotype; D050199:Podocytes / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012737:Sex Factors; D013045:Species Specificity; D013739:Testosterone / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D013739:Testosterone