Lorenzen Johan, Shah Rajshree, Biser Alisha, Staicu Serban A, Niranjan Thiruvur, Garcia Ana Maria, Gruenwald Antje, Thomas David B, Shatat Ibrahim F, Supe Katarine, Woroniecki Robert P, Susztak Katalin
Division of Nephrology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
J Am Soc Nephrol. 2008 May;19(5):884-90. doi: 10.1681/ASN.2007040486.
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.
多项基因芯片研究表明，骨桥蛋白（Opn）的表达与蛋白尿和肾小球疾病密切相关。在激素敏感型肾病综合征患者中，尿Opn浓度和肾脏Opn免疫反应性均升高。此外，在1型糖尿病肾病的Ins2（Akita）小鼠模型、脂多糖诱导的蛋白尿模型以及嘌呤霉素氨基核苷酸诱导的肾病大鼠肾小球中，肾Opn mRNA水平也升高。Opn基因敲除小鼠在注射脂多糖后未出现蛋白尿，且可免受糖尿病诱导的蛋白尿和系膜扩张影响。在肾小球中，Opn免疫染色在足细胞中特异性增加。用重组Opn处理足细胞可激活NF-κB信号通路，增加尿激酶型纤溶酶原激活剂以及基质金属蛋白酶2和9的表达，并提高足细胞的运动能力。综上所述，这些结果表明Opn可能通过调节足细胞信号传导和运动能力，在蛋白尿的发生发展中起重要作用。
