Increased expression of ephrin A1 in brain arteriovenous malformation: DNA microarray analysis

Abstract

A number of previous studies have revealed the abnormal expression of various angiogenesis-related genes or products in brain arteriovenous malformation (AVM). To understand the molecular process of this disease, we analyzed gene expression profiles in brain AVM. Using a DNA microarray consisting of 17,086 genes, we identified differentially expressed genes in 5 brain AVMs from their draining veins, vessels retaining basic venous architecture. Not many genes were differentially expressed between the AVM nidus and the draining vein. When we applied an absolute cut-off value for normalized log 2 (cy5/cy3 ratio) of 0.4, 19 genes were selected. Genes such as SOX8, TRIM2, FENA1 (ephrin A1), and AQP4 were upregulated, and genes such as I_1000105, KRT18, IGFBP7, EMILIN-2, and KRT14 were downregulated. Genes relating to angiogenesis, such as vascular endothelial growth factor and angiopoietin and other members of the ephrin family, were not differentiated. Among differentially expressed genes detected in this analysis, we focused on ephrin A1, a gene related to embryogenesis and angiogenesis. The expression of ephrin A1 was two and three to nine times higher than that of the draining vein and normal brain, respectively, using real-time reverse transcription-polymerase chain reaction. For the first time, here we report the increased expression of ephrin A1 in brain AVM, which may play an important role in the pathogenesis of AVM.

Changes in C57BL6 Mouse Hippocampal Transcriptome Induced by Hypergravity Mimic Acute Corticosterone-Induced Stress

“…The role of CTRP5 encoded by C1qtnf5-Mfrp gene is not described in the brain but it is associated with macular degeneration (Hayward et al, 2003) and lipid oxidation (Yang and Lee, 2014). If the functions of Igfn1 and Krt18 are unknown in neurons, their function in smooth muscle cells (Baker et al, 2010) and implication in intracerebral arteriovenous malformations (Sasahara et al, 2007) indicate that hypergravity could act on pericytes to modify the cerebrovascular function and hippocampus perfusion. Similarly, Sdf2l1, an endoplasmic reticulum stress-inducible gene (Fukuda et al, 2001) is implicated in the folding of proteins (Tiwari et al, 2013) but the function of the encoded proteins in brain cells (neurons, glia, and vessels) remains largely unknown.…”

Familial brain arteriovenous malformation maps to 5p13–q14, 15q11–q13 or 18p11: Linkage analysis with clipped fingernail DNA on high-density SNP array

“…We then searched for mutations in 10 genes within 5p13.2-q14.1, among which MAP3K1, DAB2 and OCLN encode proteins playing roles in the TGF- signaling pathway, and FGF10, ESM1, ITGA1, ITGA2, EGFLAM, ERBB2IP and PIK3R1 were those expressed in brain AVM tissues by previous microarray analysis [19][20][21].…”

“…On the other hand, regarding familial AVM, only two linkage analyses using 6 small families have been published by a research group [17,18], showing seven possible disease-responsible regions, i.e., 6q25 with the highest LOD score, 3p27, 4q34, 7p21, 13q32-q33, 16p13-q12 and 20q11-q13, but failed to identify the causative mutation. In sporadic brain AVM, microarray study showed that the VEGFA, ITGA5, ENG and MMP9 genes that may involve vascular development or maintenance, are highly expressed in AVM compared with normal brain parenchyma [19][20][21].…”

Mouse chromosome 17 candidate modifier genes for thrombosis

“…A recent study reports downregulation of EMILIN2 in brain arteriovenous malformations (Sasahara et al 2007). Furthermore, a number of proteomic and microarray studies of human tissues have identified EMILIN2 in extracellular fluids (plasma, amniotic, seminal, and synovial), stem cells (hematopoietic, mesenchymal, and osteoblasts), stimulated endometrial stromal cells, and cancer cells (lymphocytic leukemia, hepatic, colorectal, and ovarian cancer).…”