MicroRNA Control of Vascular Endothelial Growth Factor Signaling Output During Vascular Development

Abstract

The regulated response of endothelial cells (ECs) to signals in their environment is not only critical for the de novo formation of primordial vascular networks during early development (i.e. vasculogenesis), but is also required for the subsequent growth and remodelling of new blood vessels from pre-existing ones (i.e. angiogenesis). Vascular endothelial growth factors (Vegfs) and their endothelial-cell specific receptors play a crucial role in nearly all aspects of blood vessel growth. How the outputs from these pathways affect and coordinate endothelial behaviour is an area of intense research. Recently, numerous studies have highlighted roles for microRNAs in modulating Vegf signalling output in several different contexts. In this review we will provide an overview of how small RNAs regulate multiple aspects of the Vegf signalling pathway. In particular, we highlight areas where identification of microRNAs and their targets has provided new insight into the role of downstream effectors in modulating Vegf output during development. Since Vegf plays a broad role in multiple aspects of endothelial biology and has become a target for therapeutic manipulation of pathological blood vessel growth, microRNAs that affect Vegf signalling output will undoubtedly be major targets of clinical value.

Down-Regulation of MicroRNA-184 Is Associated With Corneal Neovascularization

“…[17][18][19] Here, we revealed by real-time PCR assay that the expression of frizzled-4 (Frz4), a member of frizzled receptor of the Wnt signaling pathway, was also upregulated in the corneal epithelia of rats after corneal suture surgery, compared with that in control rats (Fig. 1B).…”

MicroRNAs, immune cells and pregnancy

“…Regulation of angiogenesis by miRNAs occurs in both physiological and pathological conditions where both pro-and anti-angiogenic mRNAs can be targeted. 116 The most widely studied pro-angiogenic factor is VEGF, and miRNA-mediated control over angiogenesis, specifically by modulating VEGF transcripts, has been demonstrated. [117][118][119][120][121] While there are many pro-and anti-angiogenic miRNAs, each member of the miRNA-17-92 cluster (miR-17, -18a, -19a, -19b, -20a and -92a), has been shown to have anti-angiogenic effects on endothelial cell sprouting in vitro and inhibition of these miRNAs increased endothelial sprouting.…”

MicroRNAs in Endothelial Development and Differentiation

“…(Refer to Ref [14] for a thorough review). Among them, miR-126 is the most extensively studied for its role in maintaining vessel integrity and directing angiogenesis.…”

“…RISC complex finally repress mRNA translation and/or induce mRNA degradation, with the latter playing a predominant role [12]. Over the past several years, there has been an increasing amount of evidence suggesting that miRNAs are implicated in regulation of EC development, phenotype and function [13,14]. It has been suggested that miRNAs play a divergent role in EC development and differentiation from stem cells: some can maintain stem cells pluripotence, while other promote their differentiation into specific lineages depending on the targets it regulates.…”