Global expression profiling identifies a novel hyaluronan synthases 2 gene in the pathogenesis of lower extremity varicose veins
Journal
Journal of Clinical Medicine
Journal Volume
7
Journal Issue
12
Date Issued
2018
Author(s)
CHIA-SHAN HSIEH
YAU-HUNG CHEN
Abstract
Lower extremities varicose veins (VV) are among the most easily recognized venous abnormalities. The genetic mechanism of VV is largely unknown. In this study, we sought to explore the global expressional change of VV and identify novel genes that might play a role in VV. We used next-generation ribonucleic acid (RNA) sequence (RNA seq) technology to study the global messenger RNA expressional change in the venous samples of five diseased and five control patients. We identified several differentially expressed genes, which were further confirmed by conventional reverse transcription polymerase chain reaction (RT-PCR). Using these significant genes we performed in silico pathway analyses and found distinct transcriptional networks, such as angiogenesis, cell adhesion, vascular injury, and carbohydrate metabolisms that might be involved in the mechanism of VV. Among these significant genes, we also found hyaluronan synthases 2 gene (HAS2) played a pivotal role and governed all these pathways. We further confirmed that HAS2 expression was decreased in the venous samples of patients with VV. Finally, we used a zebrafish model with fluorescence emitting vasculature and red blood cells to see the morphological changes of the venous system and blood flow. We found that HAS2 knockdown in zebrafish resulted in dilated venous structural with static venous flow. HAS2 may modulate the transcriptional networks of angiogenesis, cell adhesion, vascular injury, and carbohydrate metabolisms in venous tissues and downregulation of HAS2 may underlie the mechanism of VV. © 2018 by the authors. Licensee MDPI, Basel, Switzerland.
Subjects
HAS2; RNA seq; Varicose veins
SDGs
Other Subjects
chitinase 3 like protein 1; hyaluronate synthetase; kallikrein 5; aged; angiogenesis; animal experiment; animal model; Article; bioinformatics; blood vessel injury; carbohydrate metabolism; cell adhesion; controlled study; dentate hilus; down regulation; female; gene; gene expression; gene knockdown; HAS2; human; human tissue; hyaluronan synthases 2 gene; male; nonhuman; pathogenesis; reverse transcription polymerase chain reaction; RNA extraction; RNA sequence; sequence analysis; varicosis; zebra fish
Publisher
MDPI
Type
journal article