fig2

Figure 2. Interaction of hyperglycemia-regulated thrombospondin (TSP) pathways. TSP-4 increases recruitment of macrophages, while TSP-1 is needed for the resolution of inflammation. In response to hyperglycemia, TSP-1 levels are downregulated by increased levels of miR-467. TSP-4 is upregulated as a result of upregulation of TGF-β and activation of SMAD3. Upregulation of TSP-4 result in increased recruitment of macrophages into the tumor. In the absence of TSP-1 and resolution of inflammation, the accumulation of macrophages increases. In a feedback loop, TSP-4 increases the levels of an inhibitory TGF-β receptor beta-glycan. TGF-β further decreases the production of TSP-1. In a feedback loop, TSP-1 is an activator of TGF-β. Green arrow and text = upregulation in response to hyperglycemia; red arrow and text = downregulation in response to hyperglycemia. TGF-β: transforming growth factor beta