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 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.
Lorenzen
Johan
J
Division of Nephrology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Shah
Rajshree
R
Biser
Alisha
A
Staicu
Serban A
SA
Niranjan
Thiruvur
T
Garcia
Ana Maria
AM
Gruenwald
Antje
A
Thomas
David B
DB
Shatat
Ibrahim F
IF
Supe
Katarine
K
Woroniecki
Robert P
RP
Susztak
Katalin
K
D000419:Albuminuria / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D000818:Animals; D001706:Biopsy; D002478:Cells, Cultured; D002648:Child; D003928:Diabetic Nephropathies / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009404:Nephrotic Syndrome / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D053495:Osteopontin / Q000235:genetics* / Q000378:metabolism* / Q000494:pharmacology; D010641:Phenotype; D050199:Podocytes / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology
D012333:RNA, Messenger; D011994:Recombinant Proteins; C506896:Spp1 protein, mouse; C506897:Spp1 protein, rat; D053495:Osteopontin