Platelet-derived growth factor D promotes the angiogenic capacity of endothelial progenitor cells

Neovascularization and re-endothelialization rely on endothelial progenitor cells (EPCs). However, the recruitment and angiogenic roles of EPCs are subject to regulation through the vascular microenvironment, which remains largely unknown. Platelet-derived growth factor D (PDGF-D) is a new member of the PDGF family that binds the PDGFR- homodimer. However, it remains unknown whether and how it affects the angiogenic capacity of EPCs and participates in tube-like formation. EPCs were derived from rat bone marrow cells, and the gain-of-function approach was used to study the effects of PDGF-D on the biological activities of EPCs. EPCs that stably express PDGF-D were generated by lentiviral-mediated transduction, and the expression levels were evaluated by western blotting and reverse transcription, followed by real-time quantitative polymerase chain reaction (RT-qPCR). The biological activities of EPCs evaluated in the present study included proliferation, adhesion, migration, tube formation and senescence. Furthermore, the downstream signaling of PDGF-D was explored by western blot analysis. The results revealed that the lentiviral-mediated expression of PDGF-D in the microenvironment promoted the migration, proliferation, adhesion and tube formation of EPCs. In addition, PDGF-D suppressed the senescence of EPCs. Mechanistically, PDGF-D induced the phosphorylation of several signaling molecules, including STAT3, AKT, ERK1/2, mTOR and GSK-3, suggesting that PDGF-D enhanced the angiogenic function of EPCs through PDGF receptor-dependent and -independent signaling pathways. In conclusion, PDGF-D promotes the angiogenic capacity of EPCs, including proliferation, migration, adhesion and tube formation, and thereby contributes to angiogenesis.