Differential expression of miR-145 in children with Kawasaki disease.
Differential expression of miR-145 in children with Kawasaki disease.
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DOI：
10.1371/journal.pone.0058159
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Burns JC
中科院分区：
文献类型：
--
作者：
Shimizu C;Kim J;Stepanowsky P;Trinh C;Lau HD;Akers JC;Chen C;Kanegaye JT;Tremoulet A;Ohno-Machado L;Burns JC
川崎是一种急性、自限性的儿童血管炎，可导致冠状动脉结构性损伤。先前的研究已经暗示TGF-β途径在疾病发病机制和动脉壁中肌成纤维细胞的产生中。microRNA是在转录后水平调节基因表达的小的非编码RNA，并且可以在细胞外囊泡中在细胞之间转运。为了了解microRNA在川崎中修饰基因表达的作用，我们研究了川崎病急性期和恢复期全血中的microRNA。对12例急性期和恢复期川崎患者的配对全血RNA进行了小RNA测序分析。该分析揭示了6种microRNA（miR-143、-199 b-5 p、-618、-223、-145和-145*（互补链）），其水平在川崎急性期显著升高。使用靶向qRT-PCR，使用独立队列（n = 16）验证结果。 miR-145在中性粒细胞和血管平滑肌细胞的分化中起关键作用，在急性川崎患者的血液样本中以高水平表达，而在腺病毒感染的对照患者中则没有（p = 0.005）。 在从急性川崎血浆样品中分离的小细胞外囊泡中也检测到miR-145。对6种差异表达microRNA的预测靶点进行通路分析，发现TGF-β通路是川崎病中microRNA调控的最重要通路。小RNA种类的测序允许发现可能参与川崎发病机制的microRNA。miR-145可能与其他差异表达的microRNA沿着参与急性疾病期间TGF-β途径中基因表达的调节。如果预测的靶基因得到证实，我们的研究结果表明川崎病发病机制的模型，其中miR-145调节TGF-β信号在动脉壁。
Kawasaki disease is an acute, self-limited vasculitis of childhood that can result in structural damage to the coronary arteries. Previous studies have implicated the TGF-β pathway in disease pathogenesis and generation of myofibroblasts in the arterial wall. microRNAs are small non-coding RNAs that modulate gene expression at the post-transcriptional level and can be transported between cells in extracellular vesicles. To understand the role that microRNAs play in modifying gene expression in Kawasaki disease, we studied microRNAs from whole blood during the acute and convalescent stages of the illness. RNA isolated from the matched whole blood of 12 patients with acute and convalescent Kawasaki disease were analyzed by sequencing of small RNA. This analysis revealed six microRNAs (miRs-143, -199b-5p, -618, -223, -145 and -145* (complementary strand)) whose levels were significantly elevated during the acute phase of Kawasaki disease. The result was validated using targeted qRT-PCR using an independent cohort (n = 16). miR-145, which plays a critical role in the differentiation of neutrophils and vascular smooth muscle cells, was expressed at high levels in blood samples from acute Kawasaki disease but not adenovirus-infected control patients (p = 0.005). miR-145 was also detected in small extracellular vesicles isolated from acute Kawasaki disease plasma samples. Pathway analysis of the predicted targets of the 6 differentially expressed microRNAs identified the TGF-β pathway as the top pathway regulated by microRNAs in Kawasaki disease. Sequencing of small RNA species allowed discovery of microRNAs that may participate in Kawasaki disease pathogenesis. miR-145 may participate, along with other differentially expressed microRNAs, in regulating expression of genes in the TGF-β pathway during the acute illness. If the predicted target genes are confirmed, our findings suggest a model of Kawasaki disease pathogenesis whereby miR-145 modulates TGF-β signaling in the arterial wall.
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影响因子：
14.9
作者：
Kin T;Yamada K;Terai G;Okida H;Yoshinari Y;Ono Y;Kojima A;Kimura Y;Komori T;Asai K
通讯作者：
Asai K
影响因子：
21.3
作者：
Hergenreider, Eduard;Heydt, Susanne;Dimmeler, Stefanie
通讯作者：
Dimmeler, Stefanie
影响因子：
48
作者：
Langmead, Ben;Salzberg, Steven L.
通讯作者：
Salzberg, Steven L.
影响因子：
64.8
作者：
Cordes KR;Sheehy NT;White MP;Berry EC;Morton SU;Muth AN;Lee TH;Miano JM;Ivey KN;Srivastava D
通讯作者：
Srivastava D
影响因子：
2.7
作者：
Batliner, Jasmin;Buehrer, Emanuel;Tschan, Mario P.
通讯作者：
Tschan, Mario P.