期刊
JOURNAL OF PHARMACOLOGICAL SCIENCES
卷 143, 期 4, 页码 255-263出版社
JAPANESE PHARMACOLOGICAL SOC
DOI: 10.1016/j.jphs.2020.05.003
关键词
Endometriosis; Lymphangiogenesis; Macrophage; Fibroblast; VEGFR1
资金
- Japanese Ministry of Education, Culture, Sports, Science [18H02605, 19K18704]
- Grants-in-Aid for Scientific Research [19K18704, 18H02605] Funding Source: KAKEN
Lymphangiogenesis is related to the growth of endometriosis. Here, we examined whether vascular endothelial growth factor (VEGF) receptor 1 (VEGFR1) signaling plays a role in lymphangiogenesis during endometriosis. Endometrial fragments from wild-type (WT) mice transplanted into the peritoneal wall of host WT mice (WT -> WT) developed well and displayed enhanced lymphangiogenesis associated with increases in mRNA levels of VEGF-C and VEGF-D. Compared with WT mice, the implant size and lymphangiogenesis were reduced, when endometrial fragments from mice lacking the VEGFR1 tyrosine kinase (TK) domain (TK-/-) were transplanted into host TK-/- mice (TK-/--> TK-/-). Treatment of WT -> WT mice with the VEGFR3 kinase inhibitor suppressed the size of implants and lymphangiogenesis. Immunofluorescence analyses demonstrated that VEGF-C and VEGF-D were expressed in both CD11b(+) and S100A4(+) cells. TK-/--> TK-/- mice had lower numbers of CD11b(+) and S100A4(+) cells than WT -> WT mice. When isolated bone marrow (BM)-derived macrophages or culture murine fibroblasts were stimulated with placental growth factor (PlGF), a specific agonist of VEGFR1, the levels of VEGF-C and VEGF-D were increased in a VEGFR1-dependent manner. These results suggest that VEGFR1 signaling in macrophages and fibroblasts contributes to the growth of endometrial implants and lymphangiogenesis. (C) 2020 The Authors. Production and hosting by Elsevier B.V. on behalf of Japanese Pharmacological Society.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据