Figure 6. Scheme showing hyperglycemia-induced VEGF expression regulated by PRR, RAC1, and miRNA signaling. Hyperglycemia-induced PRR activates a small GTPase RAC1 that leads to the increased expression of miR-21 via stimulation of CTGF and LOX. Increased miR-21 targeting SMAD7, SPRY1, and PTEN, and using various signaling pathways (see Discussion) regulates VEGF synthesis in ARPE-19 cells. Arrows indicate activation, and T’s indicate inhibition.