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VEGF Receptor 1-Expressing Macrophages Recruited from Bone Marrow Enhances Angiogenesis in Endometrial Tissues.
Sekiguchi, Kazuki; Ito, Yoshiya; Hattori, Kyoko; Inoue, Tomoyoshi; Hosono, Kanako; Honda, Masako; Numao, Akiko; Amano, Hideki; Shibuya, Masabumi; Unno, Nobuya; Majima, Masataka.
Afiliación
  • Sekiguchi K; Department of Pharmacology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan.
  • Ito Y; Department of Molecular Pharmacology, Graduate School of Medical Sciences, Kitasato University, Sagamihara, Kanagawa, Japan.
  • Hattori K; Department of Obstetrics and Gynecology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan.
  • Inoue T; Department of Pharmacology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan.
  • Hosono K; Department of Molecular Pharmacology, Graduate School of Medical Sciences, Kitasato University, Sagamihara, Kanagawa, Japan.
  • Honda M; Department of Pharmacology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan.
  • Numao A; Department of Molecular Pharmacology, Graduate School of Medical Sciences, Kitasato University, Sagamihara, Kanagawa, Japan.
  • Amano H; Department of Obstetrics and Gynecology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan.
  • Shibuya M; Department of Pharmacology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan.
  • Unno N; Department of Molecular Pharmacology, Graduate School of Medical Sciences, Kitasato University, Sagamihara, Kanagawa, Japan.
  • Majima M; Department of Pharmacology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan.
Sci Rep ; 9(1): 7037, 2019 05 07.
Article en En | MEDLINE | ID: mdl-31065021
Angiogenesis is critical in maintenance of endometrial tissues. Here, we examined the role of VEGF receptor 1 (VEGFR1) signaling in angiogenesis and tissue growth in an endometriosis model. Endometrial fragments were implanted into the peritoneal wall of mice, and endometrial tissue growth and microvessel density (MVD) were determined. Endometrial fragments from wild-type (WT) mice grew slowly with increased angiogenesis determined by CD31+ MVD, peaking on Day 14. When tissues from WT mice were transplanted into VEGFR1 tyrosine kinase-knockout mice, implant growth and angiogenesis were suppressed on Day 14 compared with growth of WT implants in a WT host. The blood vessels in the implants were not derived from the host peritoneum. Immunostaining for VEGFR1 suggested that high numbers of VEGFR1+ cells such as macrophages were infiltrated into the endometrial tissues. When macrophages were deleted with Clophosome N, both endometrial tissue growth and angiogenesis were significantly suppressed. Bone marrow chimera experiments revealed that growth and angiogenesis in endometrial implants were promoted by host bone marrow-derived VEGFR1+/CD11b+ macrophages that accumulated in the implants, and secreted basic fibroblast growth factor (bFGF). A FGF receptor kinase inhibitor, PD173047 significantly reduced size of endometrial tissues and angiogenesis. VEGFR1 signaling in host-derived cells is crucial for growth and angiogenesis in endometrial tissue. Thus, VEGFR1 blockade is a potential treatment for endometriosis.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neovascularización Fisiológica / Receptor 1 de Factores de Crecimiento Endotelial Vascular / Endometrio / Macrófagos Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Sci Rep Año: 2019 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neovascularización Fisiológica / Receptor 1 de Factores de Crecimiento Endotelial Vascular / Endometrio / Macrófagos Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Sci Rep Año: 2019 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Reino Unido