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From the Departments of Pharmacology,* Obstetrics and Gynecology,
Anatomy,
and Animal Sciences,
Kitasato University School of Medicine, Kanagawa; the Department of Molecular Pharmacology,|| Kitasato University Graduate School of Medical Sciences, Kanagawa; and the Department of Pharmacology,¶ Faculty of Medicine, Kyoto University, Kyoto, Japan
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.
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F. Finetti, R. Solito, L. Morbidelli, A. Giachetti, M. Ziche, and S. Donnini Prostaglandin E2 Regulates Angiogenesis via Activation of Fibroblast Growth Factor Receptor-1 J. Biol. Chem., January 25, 2008; 283(4): 2139 - 2146. [Abstract] [Full Text] [PDF] |
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