MicroRNA-29c in urinary exosome/microvesicle as a biomarker of renal fibrosis
MicroRNA-29c in urinary exosome/microvesicle as a biomarker of renal fibrosis
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尿外泌体/微泡中的 MicroRNA-29c 作为肾纤维化的生物标志物
DOI：
10.1152/ajprenal.00148.2013
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发表时间：
2013-10-01
影响因子：
4.2
通讯作者：
Liu, Bi-Cheng
中科院分区：
文献类型：
--
作者：
Lv, Lin-Li;Cao, Yu-Han;Liu, Bi-Cheng
吕玲玲，曹永华，倪浩华，徐明，刘东，刘宏，陈培，刘宝源。尿外泌体/微泡中的microRNA-29 c作为肾纤维化的生物标志物美国肾脏生理学杂志305：F1220-F1227，2013年。首次发表于2013年8月14日; doi：10.1152/ajprenal.00148.2013.-微小RNA在肾纤维化的发展中经常失调。外泌体是可以从所有肾单位节段分泌的尿液中分离的小膜囊泡。在这里，我们试图首次观察尿外泌体中的miRNA是否可以作为肾纤维化的潜在生物标志物。从32名接受肾活检的慢性肾脏病（CKD）患者和7名对照组中收集尿液样本。分离外泌体并通过外泌体标记物的免疫金染色来确认。通过RT定量PCR检测作为内源性对照的miR-29、miR-200和RNU 6 B的成员。电子显微镜证实了外泌体的典型形状，其平均尺寸为65.1 nm，并用抗CD 9和抗水通道蛋白2抗体对其进行标记。与对照相比，miR-29和miR-200的成员容易以降低的水平测量（P < 0.05），并且可以稳健地区分CKD与对照[通过受试者操作特征分析，曲线下面积（AUC）从0.902变化至1]。在CKD患者中，miR-29 c与肾小球滤过率（r = 0.362; P < 0.05）和肾小管间质纤维化程度（r = -0.359; P < 0.05）相关。此外，与中、重度肺纤维化组相比，轻度肺纤维化组外泌体中的miRNA表达减少。miR-29 a和miR-29 c可预测肾小管间质纤维化程度，AUC分别为0.883和0.738（P < 0.05）。使用miR-29 a区分轻度和中度至重度纤维化的灵敏度和特异性分别为93.8%和81.3%，使用miR-29 c区分轻度和中度至重度纤维化的灵敏度和特异性分别为68.8%和81.3%。总体而言，尿外泌体中的miR-29 c与肾功能和组织学纤维化程度相关，表明其为肾纤维化的新型非侵入性标志物。
Lv LL, Cao YH, Ni HF, Xu M, Liu D, Liu H, Chen PS, Liu BC. MicroRNA-29c in urinary exosome/microvesicle as a biomarker of renal fibrosis. Am J Physiol Renal Physiol 305: F1220-F1227, 2013. First published August 14, 2013; doi:10.1152/ajprenal.00148.2013.-Micro (mi)RNAs are frequently dysregulated in the development of renal fibrosis. Exosomes are small membrane vesicles that could be isolated from urine secreted from all nephron segments. Here we sought to observe for the first time whether miRNA in urine exosome could serve as a potential biomarker of renal fibrosis. Urine samples were collected from 32 chronic kidney disease (CKD) patients who underwent kidney biopsy and 7 controls. Exosome was isolated and confirmed by immunogold staining of exosome marker. Members of miR-29, miR-200, and RNU6B as endogenous control were detected by RT quantitative PCR. Electronic microscopy verified a typical shape of exosome with average size of 65.1 nm and labeled it with anti-CD9 and anti-aquaporin 2 antibody. Members of miR-29 and miR-200 are readily measured with reduced levels compared with controls (P < 0.05) and can robustly distinguish CKD from controls [area under the curve (AUC) varied from 0.902 to 1 by receiver operating characteristics analysis]. miR-29c correlated with both estimated glomerular filtration rate (r = 0.362; P < 0.05) and degree of tubulointerstitial fibrosis (r = -0.359; P < 0.05) for CKD patients. Moreover, miRNA in exosome was decreased in mild fibrosis group compared with moderated to severe group. miR-29a and miR-29c could predict degree of tubulointerstitial fibrosis with AUC of 0.883 and 0.738 (P < 0.05). The sensitivity and specificity for distinguishing mild from moderate to severe fibrosis were 93.8 and 81.3% with the use of miR-29a and 68.8 and 81.3% for miR-29c. Overall, miR-29c in urinary exosome correlates with both renal function and degree of histological fibrosis, suggesting it as a novel, noninvasive marker for renal fibrosis.