MicroRNAs: opening a new vein in angiogenesis research - PubMed (original) (raw)

Review

MicroRNAs: opening a new vein in angiogenesis research

Jason E Fish et al. Sci Signal. 2009.

Abstract

Activation of the angiogenic program in endothelial cells is vital for normal embryonic development and for physiological angiogenesis in the adult. In addition, angiogenesis is an important therapeutic target: Formation of new blood vessels is desirable for regenerative purposes, such as during tissue healing or transplantation, but can be pathological, as in diabetic retinopathy and cancer. The response of the vascular endothelium to angiogenic stimuli is modulated by noncoding RNAs called microRNAs. The endothelial cell-specific microRNA microRNA-126 (miR-126) promotes angiogenesis in response to angiogenic growth factors, such as vascular endothelial growth factor or basic fibroblast growth factor, by repressing negative regulators of signal transduction pathways. Additional microRNAs have been implicated in the regulation of various aspects of angiogenesis. Thus, targeting the expression of microRNAs may be a novel therapeutic approach for diseases involving excess or insufficient vasculature.

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Figures

Fig. 1

Modulation of angiogenic signaling by microRNAs. Multiple microRNAs have been implicated in controlling the angiogenic response of endothelial cells to multiple growth factors, including vascular endothelial, basic fibroblast, and epidermal growth factors. Endothelial microRNAs that promote angiogenesis include miR-126, miR-130a, miR-210, and miR-296. Known targets and regulators for each microRNA are indicated. Two endothelial microRNAs that inhibit angiogenesis are miR-221 and miR-222, which decrease the abundance of the stem cell factor ligand c-KIT. MicroRNAs present in cells that interact with the endothelium also regulate endothelial cell responses. For example, microRNAs in tumor cells promote angiogenesis by repressing thrombospondin-1 (TSP1), an antiangiogenic factor. MicroRNAs may also affect the amount of secreted growth factors, such as VEGF, released by tumor cells.

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MicroRNAs: opening a new vein in angiogenesis research - PubMed (original) (raw)