Urinary exosomal transcription factors, a new class of biomarkers for renal disease
Urinary exosomal transcription factors, a new class of biomarkers for renal disease
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DOI：
10.1038/ki.2008.206
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发表时间：
2008-09-01
影响因子：
19.6
通讯作者：
Star, Robert A.
中科院分区：
文献类型：
--
作者：
Zhou, Hua;Cheruvanky, Anita;Star, Robert A.
尿外泌体从所有肾单位节段排出，并构成细胞内肾损伤生物标志物的丰富来源。为了研究它们是否含有转录因子，我们收集了两种急性肾损伤模型（顺铂或缺血再灌注），两种足细胞损伤模型（嘌呤霉素治疗的大鼠或podocin-Vpr转基因小鼠）和局灶节段性肾小球硬化症患者，急性肾损伤和匹配的对照组的尿液。通过差速离心分离外泌体，并通过Western印迹检测发现外泌体含有激活转录因子3（ATF 3）和Wilms肿瘤1（WT-1）蛋白。这些因子存在于浓缩的外泌体部分中，但不存在于全尿中。急性损伤后，ATF 3持续存在于大鼠模型的尿外泌体中，时间早于血清肌酐的增加。在从急性肾损伤患者中分离的外泌体中发现了ATF 3，但在慢性肾病患者或对照中没有发现。尿WT-1存在于动物模型之前，显着的肾小球硬化症和9/10例局灶节段性肾小球硬化症，但没有在8个控制。我们的研究结果表明，转录因子ATF 3可能为急性肾损伤提供一种新的肾小管细胞生物标志物，而WT-1可能检测早期足细胞损伤。尿外泌体转录因子的测量可以提供对细胞调节途径的了解。
Urinary exosomes are excreted from all nephron segments and constitute a rich source of intracellular kidney injury biomarkers. To study whether they contain transcription factors, we collected urine from two acute kidney injury models (cisplatin or ischemia-reperfusion), two podocyte injury models (puromycin-treated rats or podocin-Vpr transgenic mice) and from patients with focal segmental glomerulosclerosis, acute kidney injury and matched controls. Exosomes were isolated by differential centrifugation and found to contain activating transcription factor 3 (ATF3) and Wilms Tumor 1 (WT-1) proteins detected by Western blot. These factors were found in the concentrated exosomal fraction, but not in whole urine. ATF3 was continuously present in urine exosomes of the rat models following acute injury at times earlier than the increase in serum creatinine. ATF3 was found in exosomes isolated from patients with acute kidney injury but not from patients with chronic kidney disease or controls. Urinary WT-1 was present in animal models before significant glomerular sclerosis and in 9/10 patients with focal segmental glomerulosclerosis but not in 8 controls. Our findings suggest that transcription factor ATF3 may provide a novel renal tubular cell biomarker for acute kidney injury while WT-1 may detect early podocyte injury. Measurement of urinary exosomal transcription factors may offer insight into cellular regulatory pathways.