title: CXC chemokine receptor 4 is essential for Lipo-PGE1-enhanced migration of human dermal fibroblasts.
abstract: 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.
authors.forename: Yoolhee
authors.initials: Y
authors.lastname: Yang
authors.forename: Su Kyung
authors.initials: SK
authors.lastname: Shim
authors.forename: Hyun-A
authors.initials: HA
authors.lastname: Kim
authors.forename: Mira
authors.initials: M
authors.lastname: Seon
authors.forename: Eunjung
authors.initials: E
authors.lastname: Yang
authors.forename: Daeho
authors.initials: D
authors.lastname: Cho
authors.forename: Sa Ik
authors.initials: SI
authors.lastname: Bang
mesh_terms: D000527:Alprostadil / Q000494:pharmacology*; D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D019718:Receptors, CXCR4 / Q000378:metabolism*; D014665:Vasodilator Agents / Q000494:pharmacology*; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D019718:Receptors, CXCR4; D014665:Vasodilator Agents; D000527:Alprostadil