The Role of Osteopontin in the Development of Albuminuria

Several gene array studies have suggested that osteopontin (Opn) expression strongly correlates with albuminuria and glomerular disease. Urinary Opn concentration and kidney Opn immunoreactivity were found to be increased in patients with steroid-sensitive nephrotic syndrome. In addition, renal Opn...

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Bibliographic Details
Published in:Journal of the American Society of Nephrology 2008-05, Vol.19 (5), p.884-890
Main Authors: LORENZEN, Johan, SHAH, Rajshree, WORONIECKI, Robert P, SUSZTAK, Katalin, BISER, Alisha, STAICU, Serban A, NIRANJAN, Thiruvur, GARCIA, Ana Maria, GRUENWALD, Antje, THOMAS, David B, SHATAT, Ibrahim F, SUPE, Katarine
Format: Article
Language:English
Subjects:
Albuminuria - metabolism
Albuminuria - pathology
Albuminuria - physiopathology
Animals
Biological and medical sciences
Biopsy
Brief Communications
Cells, Cultured
Child
Diabetic Nephropathies - metabolism
Diabetic Nephropathies - pathology
Diabetic Nephropathies - physiopathology
Disease Models, Animal
Humans
Male
Medical sciences
Mice
Mice, Inbred C57BL
Mice, Knockout
Nephrology. Urinary tract diseases
Nephrotic Syndrome - metabolism
Nephrotic Syndrome - pathology
Nephrotic Syndrome - physiopathology
Osteopontin - genetics
Osteopontin - metabolism
Osteopontin - pharmacology
Phenotype
Podocytes - drug effects
Podocytes - pathology
Podocytes - physiology
Rats
Rats, Sprague-Dawley
Recombinant Proteins - pharmacology
RNA, Messenger - metabolism
Signal Transduction - physiology
Urinary system involvement in other diseases. Miscellaneous
Urinary tract. Prostate gland
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Summary:Several gene array studies have suggested that osteopontin (Opn) expression strongly correlates with albuminuria and glomerular disease. Urinary Opn concentration and kidney Opn immunoreactivity were found to be increased in patients with steroid-sensitive nephrotic syndrome. In addition, renal Opn mRNA was increased in the Ins2(Akita) mouse model of type 1 diabetic nephropathy, in the LPS-induced albuminuria model, and in glomeruli of puromycin aminonucleotide-induced nephrotic rats. Opn knockout mice did not develop albuminuria in response to LPS injection, and Opn knockout mice were protected from diabetes-induced albuminuria and mesangial expansion. In the glomerulus, Opn immunostaining was increased specifically in podocytes. Treatment of podocytes with recombinant Opn activated the NF-kappaB pathway, increased expression of urokinase plasminogen activator and matrix metalloproteinases 2 and 9, and increased podocyte motility. Taken together, these results indicate that Opn plays an important role in the development of albuminuria, possibly by modulating podocyte signaling and motility.
ISSN:1046-6673
1533-3450
DOI:10.1681/asn.2007040486