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首页> 外文期刊>International Journal of Physiology, Pathophysiology and Pharmacology >Saturated fatty acids bound to albumin enhance osteopontin expression and cleavage in renal proximal tubular cells
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Saturated fatty acids bound to albumin enhance osteopontin expression and cleavage in renal proximal tubular cells

机译：结合白蛋白的饱和脂肪酸可增强骨桥蛋白在肾小管近端细胞中的表达和裂解

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Osteopontin (OPN) is one of the proinflammatory cytokines upregulated in the kidneys of diabetic animals and patients with nephropathy. An increase in urinary albumin and albumin-bound fatty acids (FA) presents a proinflammatory environment to the proximal tubules in proteinuric kidney diseases including diabetic nephropathy. This study was designed to examine if FA overload could stimulate OPN expression and cleavage in renal tubule epithelial cells. OPN gene and protein expression was examined in the kidney of Zucker diabetic (ZD) rats and cultured proximal tubular cells exposed to either bovine serum albumin (BSA) or BSA conjugated with palmitic acid (PA), the most abundant saturated plasma FA. Real-time PCR analysis confirmed an upregulation of renal cortical OPN gene correlated with albuminuria and nephropathy progression in ZD rats at the age of 7-20 weeks. Immunofluorescence staining of kidney sections revealed a massive induction of OPN protein in albumin-overloaded proximal tubules of ZD rats. A significant increase in both intact and cleaved OPN proteins was further demonstrated in the diabetic kidney and urine samples, which was attenuated by antiproteinuric treatment with losartan, an angiotensin II receptor blocker. When exposed to fatty acid-free BSA, NRK-52E cells exhibited an increase in protein levels of full-length and cleaved OPN. Moreover, the increase in OPN fragments was greatly enhanced in the presence of PA (250-500 µM). Together, our results support a stimulatory effect of albumin and conjugated FA on OPN expression and cleavage in renal tubule epithelial cells. Thus, besides lowering albuminuria/proteinuria, mitigating circulating FAs may be an effective intervention for preventing and slowing down the progression of nephropathy associated with obesity and type 2 diabetes.
机译：骨桥蛋白（OPN）是糖尿病动物和肾病患者肾脏中上调的促炎细胞因子之一。尿白蛋白和结合白蛋白的脂肪酸（FA）的增加为蛋白尿性肾脏疾病（包括糖尿病性肾病）的近端小管提供了促炎环境。这项研究旨在检查FA超负荷是否可以刺激肾小管上皮细胞中OPN的表达和裂解。在Zucker糖尿病（ZD）大鼠的肾脏中检查OPN基因和蛋白质的表达，并培养暴露于牛血清白蛋白（BSA）或与棕榈酸（PA）共轭的BSA（最丰富的饱和血浆FA）的近端肾小管细胞。实时PCR分析证实，在7-20周龄的ZD大鼠中，肾皮质OPN基因上调与白蛋白尿和肾病进展有关。肾脏切片的免疫荧光染色显示在白蛋白超载的ZD大鼠近端小管中大量诱导OPN蛋白。在糖尿病肾脏和尿液样本中，还进一步证实了完整和裂解的OPN蛋白均显着增加，这是通过使用血管紧张素II受体阻滞剂氯沙坦的抗蛋白尿治疗而减弱的。当暴露于不含脂肪酸的BSA时，NRK-52E细胞的全长和裂解的OPN蛋白质水平升高。此外，在存在PA（250-500 µM）的情况下，OPN片段的增加大大增强。在一起，我们的结果支持白蛋白和缀合的FA对肾小管上皮细胞中OPN表达和裂解的刺激作用。因此，除了降低蛋白尿/蛋白尿之外，减轻循环FAs可能是预防和减慢与肥胖症和2型糖尿病相关的肾病进展的有效干预措施。

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