Fig. 2.

Modulation of pericyte recruitment at the pericyte-EC interface. Pericyte recruitment to vascular endothelial cells (ECs) is controlled by a complex interplay between multiple signaling pathways. The schematic illustrates some of the better understood signaling cascades that affect pericyte recruitment. PDGF and EGF are released by ECs and bind to PDGFR-β and EGFR (respectively) on pericytes, stimulating pericyte migration and proliferation. S1P binds to EDG-1 expressed by pericytes and ECs, promoting pericyte migration. The Ang1/Tie2 complex enhances pericyte–EC interaction and induces the expression and release of EGF. Ang2 released by ECs binds to Tie2 on ECs and promotes pericyte-EC dissociation. TGFβ binds to TGFβR2, leading to the activation of ALK1 or ALK5. ALK1 activation stimulates pericyte recruitment while ALK5 activation results in cellular quiescence. Sema3A is released by ECs and forms a complex with Nrp1 and Plexin. This promotes enhanced EC migration and vessel remodeling. MMP9 and SPARC drive ECM remodeling, which facilitates growth factor activation and stimulates pericyte recruitment. SPARC, produced by ECs and pericytes, limits the activation of TGFβ and interferes with the ligation of PDGFR and EFGR to their respective ligands