■为了深入了解与静脉畸形(VM)有关的分子过程,并确定治疗VM的潜在目标,这项研究描述了VM中的基因表达模式,研究了VM中syndecan-1(SDC1)表达的变化,并检验了SDC1异常表达引发异常血管生成和VM发育的假设。
■进行了微阵列分析,以在VM和联合正常的转录组范围内鉴定差异表达基因(DEG)。进行了基因本体分子功能分析和京都百科全书的基因和基因组通路分析,以建立参与VM的生物信号通路的增强。在DEGs中,我们专注于SDC1,它参与了基质重塑,细胞增殖和侵袭,和血管生成。通过qRT-PCR验证了SDC1在VM中的表达,西方印迹,和免疫组织化学。通过siRNA在人脐静脉内皮细胞(HUVECs)中实现SDC1的功能丧失,以研究SDC1在细胞迁移中的作用。入侵,和血管生成。
■与对照组织相比,转录组研究确定了274个上调的DEGs和3个下调的DEGs。与正常组织相比,VM中SDC1的转录物和蛋白质水平显着降低。SDC1抑制增强HUVEC迁移,入侵,和血管生成。
■我们的全基因组微阵列分析表明VM中涉及许多基因。SDC1在血管生成和VM发育过程中起着重要作用。SDC1可能代表VM分子疗法的潜在靶标。
UNASSIGNED: To obtain insight into the molecular process implicated in venous malformations (VMs) and identify potential targets for treatment of VMs, this study profiled the gene expression pattern in VMs, investigated alterations of syndecan-1 (SDC1) expression in VMs, and tested the hypothesis that aberrant SDC1 expression triggers abnormal angiogenesis and VM development.
UNASSIGNED: Microarray analysis was performed to identify differentially expressed genes (DEGs) on a transcriptome-wide level in VMs and conjunctive normal. Gene Ontology molecular functional analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis were carried out to establish enhancement of biological signaling pathways involved in VMs. Among the DEGs, we focused on SDC1, which is involved in matrix remodeling, cell proliferation and invasion, and angiogenesis. SDC1 expression in VMs was verified by qRT-PCR, western blotting, and immunohistochemistry. Loss-of-function of SDC1 was achieved in human umbilical vein endothelial cells (HUVECs) by siRNA to investigate the roles of SDC1 in cell migration, invasion, and angiogenesis.
UNASSIGNED: Compared with control tissue, the transcriptome study identified 274 upregulated DEGs and 3 downregulated DEGs. The transcript and protein levels of SDC1 were significantly decreased in VMs compared with normal tissue. Inhibition of SDC1 enhanced HUVEC migration, invasion, and angiogenesis.
UNASSIGNED: Our genome-wide microarray analysis suggests the involvement of numerous genes in VMs. Among them, SDC1 plays a substantial role in the process of angiogenesis and development of VMs. SDC1 may represent a potential target for a molecular therapy for VMs.