VEGF Receptor 1-Expressing Macrophages Recruited from Bone Marrow Enhances Angiogenesis in Endometrial Tissues

Abstract 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...

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Autores principales:	Kazuki Sekiguchi, Yoshiya Ito, Kyoko Hattori, Tomoyoshi Inoue, Kanako Hosono, Masako Honda, Akiko Numao, Hideki Amano, Masabumi Shibuya, Nobuya Unno, Masataka Majima
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2019
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/53c1e7a7d61541b6bb4009a8327768e9
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spelling	oai:doaj.org-article:53c1e7a7d61541b6bb4009a8327768e92021-12-02T16:08:32ZVEGF Receptor 1-Expressing Macrophages Recruited from Bone Marrow Enhances Angiogenesis in Endometrial Tissues10.1038/s41598-019-43185-82045-2322https://doaj.org/article/53c1e7a7d61541b6bb4009a8327768e92019-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-43185-8https://doaj.org/toc/2045-2322Abstract 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.Kazuki SekiguchiYoshiya ItoKyoko HattoriTomoyoshi InoueKanako HosonoMasako HondaAkiko NumaoHideki AmanoMasabumi ShibuyaNobuya UnnoMasataka MajimaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-14 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Kazuki Sekiguchi Yoshiya Ito Kyoko Hattori Tomoyoshi Inoue Kanako Hosono Masako Honda Akiko Numao Hideki Amano Masabumi Shibuya Nobuya Unno Masataka Majima VEGF Receptor 1-Expressing Macrophages Recruited from Bone Marrow Enhances Angiogenesis in Endometrial Tissues
description	Abstract 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.
format	article
author	Kazuki Sekiguchi Yoshiya Ito Kyoko Hattori Tomoyoshi Inoue Kanako Hosono Masako Honda Akiko Numao Hideki Amano Masabumi Shibuya Nobuya Unno Masataka Majima
author_facet	Kazuki Sekiguchi Yoshiya Ito Kyoko Hattori Tomoyoshi Inoue Kanako Hosono Masako Honda Akiko Numao Hideki Amano Masabumi Shibuya Nobuya Unno Masataka Majima
author_sort	Kazuki Sekiguchi
title	VEGF Receptor 1-Expressing Macrophages Recruited from Bone Marrow Enhances Angiogenesis in Endometrial Tissues
title_short	VEGF Receptor 1-Expressing Macrophages Recruited from Bone Marrow Enhances Angiogenesis in Endometrial Tissues
title_full	VEGF Receptor 1-Expressing Macrophages Recruited from Bone Marrow Enhances Angiogenesis in Endometrial Tissues
title_fullStr	VEGF Receptor 1-Expressing Macrophages Recruited from Bone Marrow Enhances Angiogenesis in Endometrial Tissues
title_full_unstemmed	VEGF Receptor 1-Expressing Macrophages Recruited from Bone Marrow Enhances Angiogenesis in Endometrial Tissues
title_sort	vegf receptor 1-expressing macrophages recruited from bone marrow enhances angiogenesis in endometrial tissues
publisher	Nature Portfolio
publishDate	2019
url	https://doaj.org/article/53c1e7a7d61541b6bb4009a8327768e9
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VEGF Receptor 1-Expressing Macrophages Recruited from Bone Marrow Enhances Angiogenesis in Endometrial Tissues

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