Urinary exosomal microRNAs in incipient diabetic nephropathy.
Urinary exosomal microRNAs in incipient diabetic nephropathy.
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DOI：
10.1371/journal.pone.0073798
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Gruden G
中科院分区：
文献类型：
--
作者：
Barutta F;Tricarico M;Corbelli A;Annaratone L;Pinach S;Grimaldi S;Bruno G;Cimino D;Taverna D;Deregibus MC;Rastaldi MP;Perin PC;Gruden G
MicroRNAs （miRNAs）是一类小的非蛋白质编码rna，通过抑制靶mrna来调节基因表达。mirna以一种非常稳定的形式存在于体液中，被包装在内吞起源的微囊中，称为外泌体。在本研究中，我们评估了伴有和不伴有早期糖尿病肾病的1型糖尿病患者尿外泌体中miRNA的表达。结果显示，微量白蛋白尿患者尿外泌体中miR-130a和miR-145富集，miR-155和miR-424减少。类似地，在早期实验性糖尿病肾病的动物模型中，尿外泌体miR-145水平升高，这与肾小球内miR-145过表达相平行。将培养的系膜细胞暴露于高葡萄糖环境中，会增加系膜细胞和系膜细胞衍生外泌体中miR-145的含量，从而为糖尿病诱导的miR-145过表达提供了一种潜在的机制。总之，尿外泌体miRNA含量在伴有早期糖尿病肾病的1型糖尿病患者中发生改变，miR-145可能是该并发症中一种新的候选生物标志物/参与者。
MicroRNAs (miRNAs), a class of small non-protein-encoding RNAs, regulate gene expression via suppression of target mRNAs. MiRNAs are present in body fluids in a remarkable stable form as packaged in microvesicles of endocytic origin, named exosomes. In the present study, we have assessed miRNA expression in urinary exosomes from type 1 diabetic patients with and without incipient diabetic nephropathy. Results showed that miR-130a and miR-145 were enriched, while miR-155 and miR-424 reduced in urinary exosomes from patients with microalbuminuria. Similarly, in an animal model of early experimental diabetic nephropathy, urinary exosomal miR-145 levels were increased and this was paralleled by miR-145 overexpression within the glomeruli. Exposure of cultured mesangial cells to high glucose increased miR-145 content in both mesangial cells and mesangial cells-derived exosomes, providing a potential mechanism for diabetes-induced miR-145 overexpression. In conclusion, urinary exosomal miRNA content is altered in type 1 diabetic patients with incipient diabetic nephropathy and miR-145 may represent a novel candidate biomarker/player in the complication.
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