Thrombin treatment of HMVEC-L
RNA-seq reveals novel transcriptome of genes and their isoforms in human pulmonary microvascular endothelial cells treated with Thrombin
The regulation of endothelial functions is essential for maintaining circulatory homeostasis and the physiological function of different organs. Thrombin can stimulate endothelial cells and regulate the expression, release and activation of a number of biological mediators. However, transcriptional regulation of vascular endothelial cells by thrombin is not completely understood. In the present study, Illumina RNA-seq was used to profile the transcriptome in human pulmonary microvascular endothelial cells (HMVEC-L) treated with thrombin to gain insight into thrombin''s direct effects on the endothelial function. Out of 100 million total reads from a paired end sequencing assay, 91-94% of the reads were aligned to over 16,000 genes in the reference human genome. Thrombin upregulated 150 known genes and 480 known isoforms, and downregulated 2,190 known genes and 3,574 known isoforms by at least 2 fold. Of note, thrombin upregulated 1,775 unknown isoforms and downregulated 12,202 isoforms by at least 2 fold. Many genes displayed isoform specific differential expression levels and different usage of transcriptional start sites after the thrombin treatment. Since the dysregulation of vascular endothelial cells by different agonists including thrombin has been implicated in the development of a number of pathologic disorders, such as inflammatory conditions, cancer, diabetes, coronary heart disease, further in-depth follow-up analysis of the transcriptional regulation reported in this study may shed light on molecular pathogenic mechanisms underlying thrombin mediated endothelial dysfunction in those processes and provide new leads of potential relevant therapeutic targets.