Increased circulating miR-21 levels are associated with kidney fibrosis.
Increased circulating miR-21 levels are associated with kidney fibrosis.
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DOI：
10.1371/journal.pone.0058014
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Cauffiez C
中科院分区：
文献类型：
--
作者：
Glowacki F;Savary G;Gnemmi V;Buob D;Van der Hauwaert C;Lo-Guidice JM;Bouyé S;Hazzan M;Pottier N;Perrais M;Aubert S;Cauffiez C
microRNA（miRNAs）是一类在转录后水平上起作用以控制大量靶mRNA表达的非编码RNA。虽然有证据表明miRNAs失调在各种复杂疾病中起着致病作用，但它们在纤维化肾病中的作用在很大程度上尚未探索。在这里，我们发现miR-21在单侧输尿管梗阻小鼠的肾脏中以及严重肾纤维化患者的肾脏中强烈上调。此外，与来自正常肾脏的成纤维细胞相比，来自纤维化肾脏的小鼠原代成纤维细胞表现出更高的miR-21表达水平。正常原代肾成纤维细胞中miR-21的表达在TGFβ暴露后被诱导，TGF β是参与纤维形成的关键生长因子。最后，原代肾成纤维细胞中miR-21的异位表达足以促进肌成纤维细胞分化。由于循环miRNA已被认为是有希望的非侵入性生物标志物，我们使用来自42名肾移植受者的血清进一步评估循环miR-21水平是否与肾纤维化相关，根据其肾纤维化严重程度分类，在同种异体移植物活检中评估（间质纤维化/肾小管萎缩（IF/TA））。严重IF/TA分级患者的循环miR-21水平显著升高（IF/TA 3级：3.0±1.0 vs较低级别纤维化：1.5±1.2; p = 0.001）。 相比之下，循环miR-21水平与其他肾脏组织学病变无关。在包括IF/TA分级和估计GFR的多变量线性回归模型中，发现循环miR-21水平与IF/TA评分之间存在独立相关性（P = 0.307，p = 0.03），miR-21水平与aMDRD之间存在独立相关性（P =-0.398，p = 0.006）。 总之，这些数据表明miR-21在肾纤维化中具有关键的致病作用，并且可能代表肾纤维化的新型、预测性和可靠的血液标志物。
MicroRNAs (miRNAs) are a class of noncoding RNA acting at a post-transcriptional level to control the expression of large sets of target mRNAs. While there is evidence that miRNAs deregulation plays a causative role in various complex disorders, their role in fibrotic kidney diseases is largely unexplored. Here, we found a strong up-regulation of miR-21 in the kidneys of mice with unilateral ureteral obstruction and also in the kidneys of patients with severe kidney fibrosis. In addition, mouse primary fibroblasts derived from fibrotic kidneys exhibited higher miR-21 expression level compared to those derived from normal kidneys. Expression of miR-21 in normal primary kidney fibroblasts was induced upon TGFβ exposure, a key growth factor involved in fibrogenesis. Finally, ectopic expression of miR-21 in primary kidney fibroblasts was sufficient to promote myofibroblast differentiation. As circulating miRNAs have been suggested as promising non-invasive biomarkers, we further assess whether circulating miR-21 levels are associated with renal fibrosis using sera from 42 renal transplant recipients, categorized according to their renal fibrosis severity, evaluated on allograft biopsies (Interstitial Fibrosis/Tubular Atrophy (IF/TA). Circulating miR-21 levels are significantly increased in patients with severe IF/TA grade (IF/TA grade 3: 3.0±1.0 vs lower grade of fibrosis: 1.5±1.2; p = 0.001). By contrast, circulating miR-21 levels were not correlated with other renal histological lesions. In a multivariate linear regression model including IF/TA grade and estimated GFR, independent associations were found between circulating miR-21 levels and IF/TA score (ß = 0.307, p = 0.03), and between miR-21 levels and aMDRD (ß = −0.398, p = 0.006). Altogether, these data suggest miR-21 has a key pathogenic role in kidney fibrosis and may represent a novel, predictive and reliable blood marker of kidney fibrosis.
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影响因子：
56.9
作者：
Lagos-Quintana, M;Rauhut, R;Tuschl, T
通讯作者：
Tuschl, T
DOI：
10.1111/j.1742-4658.2010.07632.x
发表时间：
2010-05
期刊：
The FEBS journal
影响因子：
--
作者：
Jiang X;Tsitsiou E;Herrick SE;Lindsay MA
通讯作者：
Lindsay MA
影响因子：
13.6
作者：
Chung, Arthur C. K.;Huang, Xiao R.;Lan, Hui Y.
通讯作者：
Lan, Hui Y.
影响因子：
9.2
作者：
Lan HY
通讯作者：
Lan HY
影响因子：
3.7
作者：
Gilad S;Meiri E;Yogev Y;Benjamin S;Lebanony D;Yerushalmi N;Benjamin H;Kushnir M;Cholakh H;Melamed N;Bentwich Z;Hod M;Goren Y;Chajut A
通讯作者：
Chajut A