Temporal VEGFA responsive genes in HUVECs: Gene signatures and potential ligands/receptors fine-tuning angiogenesis

Abstract

Vascular Endothelial Growth Factor-A (VEGFA) signaling is crucial to the cellular processes involved in angiogenesis. Previously, we assembled a network of molecular reactions induced by VEGFA in human umbilical vein endothelial cell populations. Considering transcriptome as a read-out of the transcriptional and epigenomic regulatory network, we now present an analysis of VEGFA-induced temporal transcriptome datasets from 6 non-synchronized studies. From these datasets, applying a confidence criterion, a set of early VEGFA-responsive signature genes were derived and evaluated for their co-expression potential with respect to multiple cancer gene expression datasets. Further, inclusive of a set of ligand-receptor pairs, a list of ligand and receptor signaling systems that potentially fine-tune the endothelial cell functions subsequent to VEGFA signaling were also derived. We believe that a number of these signaling systems would concurrently and/or hierarchically fine-tune the signaling network of endothelial cell populations towards the processes associated with angiogenesis through autocrine, paracrine, juxtacrine, and matricrine modes. By further analysis of published literature on VEGFA signaling, we also present an improved update-version of our previous VEGFA signaling network model in endothelial cells as a platform for analysis of crosstalk with these signaling systems.

Endothelial Notch signaling directly regulates the small GTPase RND1 to facilitate Notch suppression of endothelial migration

“…Thus, we identified several other Notch target genes that rapidly respond to diverse means of Notch activation and whose regulatory elements include likely endothelial Notch-responsive enhancer elements, although their roles in angiogenesis are not clear in all cases. Several of the genes identified, such as KCNJ2 and LMO2 respond to VEGF-A 38 – 41 , suggesting that VEGF-induced activation of Notch signaling is critical for their regulation. SAT1 is enriched in tumor endothelial stalk cells, where Notch signaling is highly active 42 , and encodes a key regulator of polyamine content 43 , suggesting it may participate in Notch control of endothelial metabolism.…”

Protrudin regulates FAK activation, endothelial cell migration and angiogenesis

“…Figure 3 c demonstrates gene expression alterations for some of the key molecules downstream of VEGF-triggered VEGFR2 phosphorylation that regulate EC migration. VEGF-VEGFR2 signaling network as indicated in Wikipathways was used as a reference to plot this signaling network ( https://www.wikipathways.org/index.php/Pathway:WP3888 ) [ 46 , 47 ].…”

Identification of Hub Genes and Key Pathways Associated with Anti-VEGF Resistant Glioblastoma Using Gene Expression Data Analysis

“…We have identified 21 hub genes with hybrid centrality score > 12, among which 10 were up- and 11 downregulated. The possible role of these hub genes in the development of anti VEGF resistance in GBM was suggested from the data showing interaction of 18 of these hub genes with 58 genes of different network modules in the VEGF - mediated angiogenesis signaling pathway [ 6 , 67 ]. In this context, our previous report on multiple phytochemicals of a poly-herbal formulation targeting multiple components of VEGF - VEGFR2 pathway and inhibiting angiogenesis is particularly significant [ 68 ].…”