miR-29c in urinary exosomes as predictor of early renal fibrosis in lupus nephritis
miR-29c in urinary exosomes as predictor of early renal fibrosis in lupus nephritis
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DOI：
10.1093/ndt/gfv128
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发表时间：
2015-09-01
影响因子：
6.1
通讯作者：
Ordi-Ros, Josep
中科院分区：
文献类型：
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作者：
Sole, Cristina;Cortes-Hernandez, Josefina;Ordi-Ros, Josep
尽管预后总体改善，10-30%的狼疮性肾炎（LN）患者会发展为终末期肾脏疾病。迄今为止，肾活检仍然是预测肾脏预后的“金标准”检查。然而，由于其侵入性，需要新的非侵入性生物标志物。尿外泌体是由每个面向尿空间的上皮细胞释放的微泡，是肾功能障碍和损伤的理想标记来源。在这里，我们试图评估miR-29c在尿外泌体中的表达水平，作为LN肾纤维化的一种新的生物标志物。从32例活检证实的LN患者、15例非狼疮慢性肾脏疾病患者和20例健康对照者中分离出尿外泌体。利用电镜和western blot对外泌体进行表征。RT-PCR定量检测miR-29c的表达水平，并与临床和组织学参数以及Smad2/3、tgf - β和MMP2/9的表达水平相关。为了比较，我们还对尿小球中的miRNA表达进行了评估。尿外泌体中MiR-29c水平与组织慢性指数（r = -0.898, P = 0.001）和肾小球硬化（r = -0.555, P = 0.007）呈强负相关。与eGFR和肌酐水平无相关性。MiR-29c表达水平可预测LN患者的慢性程度，曲线下面积（AUC）为0.946 (P < 0.001)，具有较高的敏感性和特异性（94%和82%）。尿外泌体中Smad3和MMP2的表达与miR-29c的表达呈负相关（r分别= -0.737和-0.856）。尿小球中未检测到miR-29c的表达；然而，Smad3和MMP2的表达上调（分别增加3.54倍和5.85倍）。总体而言，miR-29c与肾脏慢性程度相关，但与肾功能无关，这表明它可以作为LN患者早期纤维化进展的一种新的非侵入性标志物。
Despite overall improvement in prognosis, 10-30% of patients with lupus nephritis (LN) will develop end-stage renal disease. To date, renal biopsy is still the 'gold standard' test used to predict renal outcome. However, due to its invasive nature, new non-invasive biomarkers are required. Urinary exosomes, microvesicles released by every epithelial cell facing the urinary space, represent an ideal source of markers for renal dysfunction and injury. Here, we sought to evaluate miR-29c expression levels in urinary exosomes as a novel biomarker of renal fibrosis in LN.Urinary exosomes were isolated from 32 samples of patients with biopsy-proven LN, 15 non-lupus chronic kidney diseases and 20 healthy controls. Electronic microscopy and western blot were used to characterize the exosomes. Expression levels of miR-29c were detected by RT-PCR quantitative and correlated with clinical and histological parameters along with the expression levels of Smad2/3, TGF-beta and MMP2/9. For comparison, miRNA expression was also evaluated in the urinary pellet.MiR-29c levels in urinary exosomes showed a negatively strong correlation with the histological chronicity index (r = -0.898, P = 0.001) and glomerular sclerosis (r = -0.555, P = 0.007). No correlation with eGFR and creatinine levels was found. MiR-29c expression levels could predict the degree of chronicity in patients with LN with an area under the curve (AUC) of 0.946 (P < 0.001) and with high sensitivity and specificity (94% and 82%). Smad3 and MMP2 expression in urinary exosomes correlated negatively with miR-29c expression (r = -0.737 and -0.856, respectively). In the urinary pellet, no miR-29c expression was detected; however, upregulation of Smad3 and MMP2 was observed (3.54- and 5.85-fold increase).Overall, miR-29c correlated with the degree of renal chronicity but not with renal function, suggesting it could be used as a novel non-invasive marker of early progression to fibrosis in patients with LN.