1. Recruitment of a prostaglandin E receptor subtype, EP3-expressing bone marrow cells is crucial in wound-induced angiogenesis.
- Author
-
Kamoshita E, Ikeda Y, Fujita M, Amano H, Oikawa A, Suzuki T, Ogawa Y, Yamashina S, Azuma S, Narumiya S, Unno N, and Majima M
- Subjects
- Animals, Antibodies pharmacology, Bone Marrow Transplantation, Dermatologic Surgical Procedures, Endothelial Growth Factors administration & dosage, Endothelial Growth Factors antagonists & inhibitors, Endothelial Growth Factors metabolism, Mice, Mice, Knockout, Platelet Endothelial Cell Adhesion Molecule-1 analysis, Receptors, Prostaglandin E genetics, Receptors, Prostaglandin E, EP3 Subtype, Signal Transduction, Skin cytology, Bone Marrow Cells metabolism, Neovascularization, Physiologic drug effects, Neovascularization, Physiologic genetics, Receptors, Prostaglandin E metabolism, Skin blood supply, Wound Healing drug effects, Wound Healing genetics
- Abstract
E-type prostaglandins have been reported to be proangiogenic in vivo. Thus, we examined prostaglandin receptor signaling relevant to wound-induced angiogenesis. Full-thickness skin wounds were created on the backs of mice, and angiogenesis in wound granulation tissues was estimated. Wound closure and re-epithelization in EP3 receptor knockout mice (EP3-/-) were significantly delayed compared with their wild-type (WT) mice, whereas those in EP1-/-, EP2-/-, and EP4-/- were not delayed. Wound-induced angiogenesis estimated with CD31 immunohistochemistry in EP3-/- mice was significantly inhibited compared with that in WT mice. Immunoreactive vascular endothelial growth factor (VEGF) in wound granulation tissues in EP3-/- mice was markedly less than that in WT mice. Wound closure in WT mice was delayed significantly by VEGF neutralizing antibody compared with control IgG. Wound-induced angiogenesis and wound closure were significantly suppressed in EP3-/- bone marrow transplantation mice compared with those in WT bone marrow transplantation mice. These were accompanied with the reductions in accumulation of VEGF-expressing cells in wound granulation tissues and in mobilization of VEGF receptor 1-expressing leukocytes in peripheral circulation. These results indicate that the recruitment of EP3-expressing cells to wound granulation tissues is critical for surgical wound healing and angiogenesis via up-regulation of VEGF.
- Published
- 2006
- Full Text
- View/download PDF