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

초록

Lipo-PGE1 [EGLANDIN (R); 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-PGE1enhanced HDF migration. Moreover, Lipo-PGE1 directly induced the phosphorylation of c-Jun N-terminal kinase (JNK), and the JNK-specific inhibitor Sp6000125 blocked Lipo-PGE1enhanced 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.

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