TY - JOUR
T1 - The role of osteopontin in the development of albuminuria
AU - Lorenzen, Johan
AU - Shah, Rajshree
AU - Biser, Alisha
AU - Staicu, Serban A.
AU - Niranjan, Thiruvur
AU - Garcia, Ana Maria
AU - Gruenwald, Antje
AU - Thomas, David B.
AU - Shatat, Ibrahim F.
AU - Supe, Katarine
AU - Woroniecki, Robert P.
AU - Susztak, Katalin
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2008/5
Y1 - 2008/5
N2 - 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.
AB - 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.
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U2 - 10.1681/ASN.2007040486
DO - 10.1681/ASN.2007040486
M3 - Article
C2 - 18443355
AN - SCOPUS:44049104885
VL - 19
SP - 884
EP - 890
JO - Journal of the American Society of Nephrology
JF - Journal of the American Society of Nephrology
SN - 1046-6673
IS - 5
ER -