CXC chemokine receptor 4 is essential for Lipo-PGE1-enhanced migration of human dermal fibroblasts

: Lipo‐PGE1 [EGLANDIN®; a lipid microsphere‐incorporated prostaglandin E1 (PGE1)] stimulates angiogenesis and promotes the healing of skin ulcers. Because the effects of Lipo‐PGE1 on cutaneous wound healing are not completely understood, we investigated the ability of Lipo‐PGE1 to affect in vivo wound healing and regulate the migration of human dermal fibroblasts (HDFs). In a murine wound model, Lipo‐PGE1 reduced the wound size compared with control mice. Lipo‐PGE1 significantly increased HDF migration in a dose‐ and time‐dependent manner. Lipo‐PGE1 markedly increased the expression of CXC chemokine receptor 4 (CXCR4), which controls the migration of HDFs, at the mRNA and protein levels. Small interfering RNA (siRNA)‐mediated knockdown of CXCR4 inhibited Lipo‐PGE1–enhanced HDF migration. Moreover, Lipo‐PGE1 directly induced the phosphorylation of c‐Jun N‐terminal kinase (JNK), and the JNK‐specific inhibitor Sp6000125 blocked Lipo‐PGE1–enhanced migration and CXCR4 expression of HDFs. Our results demonstrate that Lipo‐PGE1 accelerates wound healing in vivo and increases the CXCR4‐mediated migration of HDFs through the JNK pathway.