Renal Diagnostics and Therapeutics Unit, NIDDK, National Institutes of Health, 10 Center Dr., Bldg 10, Rm. 3N108, Bethesda, MD 20892-1268.
Am J Physiol Renal Physiol. 2013 Aug 15;305(4):F553-9. doi: 10.1152/ajprenal.00056.2013. Epub 2013 Jun 12.
Renal Wilms' tumor-1 (WT-1) staining is used to detect podocyte loss in kidney biopsies. We aimed to determine if urinary exosomal WT-1 could serve as a noninvasive biomarker of podocyte injury. We examined WT-1 by Western blot in a human podocyte-like cell line, a mouse model of podocyte injury, and human subjects with podocyte disorders. WT-1 was detected in exosomal fraction of the conditioned media from podocytes and increased 48 h after hTGF-β1 stimulation. Cellular WT-1 decreased in podocytes following hTGF-β1 incubation. In mice with induced podocyte injury, urinary exosomal WT-1 was detected 1 wk earlier than albuminuria and also tracked the effects of angiotensin receptor blocker (ARB) treatment. In addition, urinary exosomal WT-1 levels at 1 wk post-injury correlated with the severity of glomerular injury at 3 wk later. In human subjects, urinary exosomal WT-1 was significantly increased in focal segmental glomerulosclerosis (FSGS) patients compared with healthy volunteers or steroid-sensitive nephrotic syndrome (SSNS) patients. Urinary exosomal WT-1 was also significantly decreased in patients in remission for either FSGS or SSNS or following steroid treatment in six SSNS subjects. We conclude that urinary exosomal WT-1 is a promising noninvasive biomarker with apparent podocyte specificity that can detect early progression and treatment-induced regression of podocyte injury in FSGS or SSNS. These results warrant longitudinal, prospective studies in a large cohort with a range of podocyte diseases.
肾母细胞瘤 1 号（WT-1）染色用于检测肾活检中足细胞的丢失。我们旨在确定尿外泌体 WT-1 是否可作为足细胞损伤的非侵入性生物标志物。我们通过 Western blot 在人足细胞样细胞系、足细胞损伤的小鼠模型和足细胞疾病患者中检查 WT-1。WT-1 存在于足细胞条件培养基的外泌体部分中，并在 hTGF-β1 刺激后 48 小时增加。hTGF-β1 孵育后，足细胞中的细胞 WT-1 减少。在诱导的足细胞损伤的小鼠中，尿外泌体 WT-1 比白蛋白尿更早被检测到，并且还跟踪了血管紧张素受体阻滞剂（ARB）治疗的效果。此外，损伤后 1 周的尿外泌体 WT-1 水平与 3 周后肾小球损伤的严重程度相关。在人类受试者中，与健康志愿者或类固醇敏感性肾病综合征（SSNS）患者相比，局灶节段性肾小球硬化症（FSGS）患者的尿外泌体 WT-1 显着增加。FSGS 或 SSNS 缓解或六例 SSNS 患者接受类固醇治疗后，尿外泌体 WT-1 也显着降低。我们得出结论，尿外泌体 WT-1 是一种有前途的非侵入性生物标志物，具有明显的足细胞特异性，可检测 FSGS 或 SSNS 中足细胞损伤的早期进展和治疗诱导的缓解。这些结果需要在具有一系列足细胞疾病的大队列中进行纵向、前瞻性研究。
