The role of osteopontin in the development of albuminuria

Johan Lorenzen, Rajshree Shah, Alisha Biser, Serban A. Staicu, Thiruvur Niranjan, Ana Maria Garcia, Antje Gruenwald, David B. Thomas, Ibrahim F. Shatat, Katarine Supe, Robert P. Woroniecki, Katalin Susztak

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Abstract

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 Ins2Akita 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-κB 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.

Original languageEnglish (US)
Pages (from-to)884-890
Number of pages7
JournalJournal of the American Society of Nephrology
Volume19
Issue number5
DOIs
StatePublished - May 1 2008

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ASJC Scopus subject areas

  • Nephrology

Cite this

Lorenzen, J., Shah, R., Biser, A., Staicu, S. A., Niranjan, T., Garcia, A. M., Gruenwald, A., Thomas, D. B., Shatat, I. F., Supe, K., Woroniecki, R. P., & Susztak, K. (2008). The role of osteopontin in the development of albuminuria. Journal of the American Society of Nephrology, 19(5), 884-890. https://doi.org/10.1681/ASN.2007040486