Urinary Smad1 is a novel marker to predict later onset of mesangial matrix expansion in diabetic nephropathy
Urinary Smad1 is a novel marker to predict later onset of mesangial matrix expansion in diabetic nephropathy
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DOI：
10.2337/db07-1726
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发表时间：
2008-06-01
期刊：
影响因子：
7.7
通讯作者：
Doi, Toshio
中科院分区：
文献类型：
--
作者：
Mima, Akira;Arai, Hidenori;Doi, Toshio
我们报道Smad 1是糖尿病肾病系膜基质扩张的关键转录因子。在这项研究中，我们研究了尿Smad 1在糖尿病的早期阶段是否可以预测以后的发展肾小球硬化症的糖尿病肾病和血管紧张素II 1型受体阻滞剂（ARB）如何可以调节结构的变化和尿markers.RESEARCH设计和方法-Smad 1和尿白蛋白进行了检查后4周注射链脲佐菌素在48只大鼠或6周的糖尿病db/db小鼠。在大鼠中20周或小鼠中12周后分析它们的肾脏病理学。48只糖尿病大鼠中7只给予奥美沙坦治疗20周，糖尿病大鼠4周时尿Smad 1与24周时系膜基质扩张呈良好相关（r = 0.70，P < 0.001），而蛋白尿相关性较弱（r = 0.31，P = 0.043）。奥美沙坦治疗显著改善肾小球硬化，并显著降低尿Smad 1（从3.9 +/- 2.9至0.3 +/- 0.3 ng/mg肌酐，P < 0.05）。在db/db小鼠中，6周时的尿Smad 1也与1周时的系膜扩张显著相关。与此相反，在控制糖尿病大鼠或mice.CONCLUSIONS-The尿Smad 1在糖尿病的早期阶段的增加与肾小球硬化症在两个啮齿类动物模型的后期发展没有变化。这些数据表明，尿Smad 1可能是一种新的预测后期发病的形态学变化，并可用于监测ARB在糖尿病肾病的影响。
OBJECTIVE-We reported that Smad1 is a key transcriptional factor for mesangial matrix expansion in diabetic nephropathy. In this study, we examined whether urinary Smad1 in an early phase of diabetes can predict later development of glomerulosclerosis in diabetic nephropathy and how an angiotensin II type 1 receptor blocker (ARB) can modulate structural changes and urinary markers.RESEARCH DESIGN AND METHODS-Smad1 and albumin in the urine were examined 4 weeks after injection of streptozotocin in 48 rats or 6 weeks of diabetes in db/db mice. Their renal pathology was analyzed after 20 weeks in rats or 12 weeks in mice. Among 48 diabetic rats 7 rats were treated with olmesartan for 20 weeks.RESULTS-Urinary Smad1 of diabetic rats at 4 weeks was nicely correlated with mesangial matrix expansion at 24 weeks (r = 0.70, P < 0.001), while albuminuria showed a weaker association (r = 0.31, P = 0.043). Olmesartan treatment significantly ameliorated glomerulosclerosis and dramatically decreased urinary Smad1 (from 3.9 +/- 2.9 to 0.3 +/- 0.3 ng/mg creatinine, P < 0.05). In db/db mice, urinary Smad1 at 6 weeks was also significantly correlated with mesangial expansion at 1 weeks. In contrast, there was no change in urinary Smad1 in control diabetic rats or mice.CONCLUSIONS-The increase of urinary Smad1 in the early stages of diabetes is correlated with later development of glomerulosclerosis in two rodent models. These data indicate that urinary Smad1 could be a novel predictor for later onset of morphological changes and can be used to monitor the effect of ARBs in diabetic nephropathy.