Interactome of miRNAs and transcriptome of human umbilical cord endothelial cells exposed to short-term simulated microgravity.
Dharanibalan KasiviswanathanRajadurai C PerumalSrinivasan BhuvaneswariPavitra KumarLakshmikirupa SundaresanManuel PhilipSajesh Puthenpurackal KrishnankuttySuvro ChatterjeePublished in: NPJ microgravity (2020)
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.
Keyphrases
- endothelial cells
- cell proliferation
- cell cycle
- high glucose
- umbilical cord
- long non coding rna
- mesenchymal stem cells
- vascular endothelial growth factor
- nitric oxide
- long noncoding rna
- gene expression
- cell adhesion
- pi k akt
- wound healing
- induced apoptosis
- oxidative stress
- signaling pathway
- pluripotent stem cells
- dna methylation
- hydrogen peroxide
- cancer therapy
- cell cycle arrest
- nitric oxide synthase
- clinical practice