Hsieh Chia-Shan, Tsai Chia-Ti, Chen Yau-Hung, Chang Sheng-Nan, Hwang Juey-Jen, Chuang Eric Y, Wu I-Hui
Department of Life Science, Genome and Systems Biology Degree Program, National Taiwan University, Taipei 10617, Taiwan.
Bioinformatics and Biostatistics Core, Center of Genomic Medicine, National Taiwan University, Taipei 10055, Taiwan.
J Clin Med. 2018 Dec 11;7(12):537. doi: 10.3390/jcm7120537.
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 () played a pivotal role and governed all these pathways. We further confirmed that 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 knockdown in zebrafish resulted in dilated venous structural with static venous flow. may modulate the transcriptional networks of angiogenesis, cell adhesion, vascular injury, and carbohydrate metabolisms in venous tissues and downregulation of may underlie the mechanism of VV.
下肢静脉曲张是最容易识别的静脉异常之一。静脉曲张的遗传机制在很大程度上尚不清楚。在本研究中，我们试图探索静脉曲张的整体表达变化，并鉴定可能在静脉曲张中起作用的新基因。我们使用下一代核糖核酸（RNA）测序（RNA seq）技术来研究5例患病患者和5例对照患者静脉样本中的整体信使RNA表达变化。我们鉴定了几个差异表达基因，这些基因通过传统逆转录聚合酶链反应（RT-PCR）进一步得到证实。利用这些重要基因，我们进行了计算机通路分析，发现了不同的转录网络，如血管生成、细胞粘附、血管损伤和碳水化合物代谢，这些可能参与了静脉曲张的机制。在这些重要基因中，我们还发现透明质酸合酶2基因（）起关键作用并调控所有这些通路。我们进一步证实，在静脉曲张患者的静脉样本中，该基因的表达降低。最后，我们使用具有荧光发射血管系统和红细胞的斑马鱼模型来观察静脉系统的形态变化和血流情况。我们发现，在斑马鱼中敲低该基因会导致静脉结构扩张且静脉血流停滞。该基因可能调节静脉组织中血管生成、细胞粘附、血管损伤和碳水化合物代谢的转录网络，其下调可能是静脉曲张机制的基础。
