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Interactome of miRNAs and transcriptome of human umbilical cord endothelial cells exposed to short-term simulated microgravity.
npj Microgravity ( IF 4.4 ) Pub Date : 2020-07-30 , DOI: 10.1038/s41526-020-00108-6
Dharanibalan Kasiviswanathan 1, 2 , Rajadurai Chinnasamy Perumal 3 , Srinivasan Bhuvaneswari 1, 2 , Pavitra Kumar 1 , Lakshmikirupa Sundaresan 1, 2 , Manuel Philip 3 , Sajesh Puthenpurackal Krishnankutty 3 , Suvro Chatterjee 1, 2
Affiliation  

Adaptation of humans in low gravity conditions is a matter of utmost importance when efforts are on to a gigantic leap in human space expeditions for tourism and formation of space colonies. In this connection, cardiovascular adaptation in low gravity is a critical component of human space exploration. Deep high-throughput sequencing approach allowed us to analyze the miRNA and mRNA expression profiles in human umbilical cord vein endothelial cells (HUVEC), cultured under gravity (G), and stimulated microgravity (MG) achieved with a clinostat. The present study identified totally 1870 miRNAs differentially expressed in HUVEC under MG condition when compared to the cells subjected to unitary G conditions. The functional association of identified miRNAs targeting specific mRNAs revealed that miRNAs, hsa-mir-496, hsa-mir-151a, hsa-miR-296-3p, hsa-mir-148a, hsa-miR-365b-5p, hsa-miR-3687, hsa-mir-454, hsa-miR-155-5p, and hsa-miR-145-5p differentially regulated the genes involved in cell adhesion, angiogenesis, cell cycle, JAK-STAT signaling, MAPK signaling, nitric oxide signaling, VEGF signaling, and wound healing pathways. Further, the q-PCR based experimental studies of upregulated and downregulated miRNA and mRNAs demonstrate that the above reported miRNAs influence the cell proliferation and vascular functions of the HUVEC in MG conditions effectively. Consensus on the interactome results indicates restricted fluctuations in the transcriptome of the HUVEC exposed to short-term MG that could lead to higher levels of endothelial functions like angiogenesis and vascular patterning.



中文翻译:

暴露于短期模拟微重力的人脐带内皮细胞的 miRNA 和转录组的相互作用。

当人类努力实现人类太空探险旅游和太空殖民地形成的巨大飞跃时,人类在低重力条件下的适应是至关重要的。在这方面,低重力下的心血管适应是人类太空探索的关键组成部分。深度高通量测序方法使我们能够分析在重力 (G) 下培养和使用回转器实现的刺激微重力 (MG) 下培养的人脐带静脉内皮细胞 (HUVEC) 中的 miRNA 和 mRNA 表达谱。本研究鉴定出 MG 条件下的 HUVEC 与单一 G 条件下的细胞相比,总共有 1870 个 miRNA 存在差异表达。已识别的针对特定 mRNA 的 miRNA 的功能关联揭示了 miRNA、hsa-mir-496、hsa-mir-151a、hsa-miR-296-3p、hsa-mir-148a、hsa-miR-365b-5p、hsa-miR -3687、hsa-mir-454、hsa-miR-155-5p 和 hsa-miR-145-5p 差异调节参与细胞粘附、血管生成、细胞周期、JAK-STAT 信号传导、MAPK 信号传导、一氧化氮信号传导的基因、 VEGF 信号传导和伤口愈合途径。此外,基于 q-PCR 的上调和下调 miRNA 和 mRNA 的实验研究表明,上述报道的 miRNA 在 MG 条件下有效影响 HUVEC 的细胞增殖和血管功能。相互作用组结果的共识表明,暴露于短期 MG 的 HUVEC 转录组波动有限,可能导致血管生成和血管模式等内皮功能水平升高。

更新日期:2020-07-30
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