Metabolic Syndrome Is Associated With Altered mRNA and miRNA Content in Human Circulating Extracellular Vesicles.
Metabolic Syndrome Is Associated With Altered mRNA and miRNA Content in Human Circulating Extracellular Vesicles.
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DOI：
10.3389/fendo.2021.687586
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发表时间：
2021
影响因子：
5.2
通讯作者：
Lerman LO
中科院分区：
文献类型：
--
作者：
Li Y;Meng Y;Zhu X;Van Wijnen A;Eirin A;Lerman LO
作为细胞间通讯的介质，循环细胞外载体（EVs）可以通过改变受体细胞的转录谱来调节组织和细胞通路，其含量可能反映其亲本细胞的状态。然而，他们的货物是否在代谢综合征（Mets）中改变仍不清楚。我们假设met改变了循环ev内包装的mrna和mirna。从MetS患者或年龄匹配的Lean对照（各n=4）的血浆中收集ev。进行RNA测序以鉴定失调的mrna和mirna，并分析mirna靶向的基因、顶级途径和与met - ev相关的疾病。MetS患者表现出体重、血压、血糖、胰岛素和肝损伤标志物水平升高。与lean - ev相比，MetS- ev中有1,446个mrna下调，32个mrna上调，而MetS- ev中有40个mirna选择性富集，10个mirna下调。MetS上调了参与细胞凋亡、线粒体调节、运输和脂蛋白的EVs基因，但下调了血管和心脏发育、蛋白质复合物生物发生和血管生成。MetS还上调了与细胞过程（包括氧化还原）相关的靶向基因的mirna，并下调了能够调节催化活性、心脏、血管和骨骼发育、转录调控、凋亡和细胞周期的mirna。因此，我们的研究表明，患有MetS的人类受试者显示循环ev的货物被修改，这反过来可能调节几个关键的细胞功能和命运。这些ev可能反映了其亲本细胞的异常状态，并可能在MetS的进展和治疗中作为重要的调节剂、生物标志物和靶点。
As mediators of intercellular communication, circulating extracellular vehicles (EVs) can modulate tissue and cellular pathways by altering transcription profiles in recipient cells, and their content may reflect the status of their parent cells. However, whether their cargo is altered in the metabolic syndrome (Mets) remains unclear. We hypothesized that MetS altered mRNAs and miRNAs packed within circulating-EVs. EVs were collected from plasma of patients with MetS or age-matched Lean controls (n=4 each). RNA sequencing was performed to identify dysregulated mRNAs and miRNAs, and analyze genes targeted by miRNAs, top pathways, and diseases associated with MetS-EVs. MetS patients showed elevated body weight, blood pressure, glucose, insulin, and liver injury markers levels. 1,446 mRNAs were downregulated and 32 upregulated in MetS- compared to Lean-EVs, whereas 40 miRNAs were selectively enriched and 10 downregulated in MetS-EVs. MetS upregulated in EVs genes involved in apoptosis, mitochondrial regulation, transport, and lipoproteins, but downregulated vessel and heart development, protein complex biogenesis, and angiogenesis. MetS also upregulated miRNAs targeting genes implicated in cellular processes, including oxidation–reduction, and downregulated miRNAs capable of modulating catalytic activity, as well as heart, blood vessel, and skeletal development, transcriptional regulation, apoptosis, and cell cycle. Our study, thus, indicates that human subjects with MetS show modified cargo of circulating EVs, which in turn may modulate several critical cellular functions and fate. These EVs may reflect the anomalous status of their parent cells, and potentially serve as important regulators, biomarkers, and targets in the progression and treatment of MetS.
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影响因子：
64.5
作者：
Crewe C;Joffin N;Rutkowski JM;Kim M;Zhang F;Towler DA;Gordillo R;Scherer PE
通讯作者：
Scherer PE
影响因子：
6.1
作者：
Singh N;Lawana V;Luo J;Phong P;Abdalla A;Palanisamy B;Rokad D;Sarkar S;Jin H;Anantharam V;Kanthasamy AG;Kanthasamy A
通讯作者：
Kanthasamy A
影响因子：
2.7
作者：
Eirin, Alfonso;Hedayat, Ahmad F.;Lerman, Lilach O.
通讯作者：
Lerman, Lilach O.
影响因子：
3.8
作者：
Ramzan, F.;D'Souza, R. F.;Cameron-Smith, D.
通讯作者：
Cameron-Smith, D.
影响因子：
4.6
作者：
Eirin A;Zhu XY;Puranik AS;Woollard JR;Tang H;Dasari S;Lerman A;van Wijnen AJ;Lerman LO
通讯作者：
Lerman LO