Abstract
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‑β 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‑3β, 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.