Figure 7

Hypothesis on the possible mechanisms of the pro-angiogenic effect produced by NSPCs. A: general mechanism of the NSPC-supported EC morphogenesis. NSPC-released pro-angiogenic factors induce changes in miRNA and gene expression in ECs, leading to activation of cell signaling pathways regulating EC morphogenesis and blood vessel formation. Panel B: a possible link between NSPC signaling and alterations in EC miRNA expression, leading to endothelial morphogenesis. NSPC-released pro-angiogenic factors such as VEGF, TGF-β and TNF, etc., bind to the corresponding receptors on EC surfaces, and trigger the activation of transcriptional or post-transcriptional supressors of miRNA 155, 100, and let-7i expression. Resulting downregulation (blue arrow) of miR-155, miR-100, and miR-let-7i leads to the increased (red arrow) expression of mTOR, SMAD2, and SMAD3, and thus activation of the mTOR and TGF-β signaling cascade and transcription of genes responsible for endothelial morphogenesis.