麻豆精品视频在线_韩国三级av_亚洲一区中文_涩涩的网址_91极品尤物_日本猛少妇色xxxxx_在线性视频_亚洲第一综合_大牛影视剧免费播放在线_被触手肉干高h潮文

Role of VEGFR3 ligand-binding domain-mediated signals in lymphangiogenesis and homeostasis

• 1、Cyrus Tang Hematology Center,Soochow University,Suzhou 215123

Abstract：Objective: While vascular endothelial growth factor receptor-3 (VEGFR3) is known to play a critical role in lymphangiogenesis, its ligand-binding domain (LBD)-mediated signaling in lymphangiogenesis and homeostasis, particularly in different tissues, remain to be fully elucidated. Methods: We employed a genetically modified mouse model targeting the LBD of VEGFR3in this study. The induced gene deletion was performed at different developmental stages, including neonatal, juvenile and adult stages. Tissues including skin, trachea, intestine, and diaphragm from the mutant and control mice were collected for the analysis of lymphatic vessels. Results: Immunofluorescence staining revealed that the induced deletion of the VEGFR3LBD at the neonatal stage (P1-4) suppressed lymphangiogenesis in several tissues examined. There was a significant decrease of lymphatic vessel density in the abdominal as well as the tail skin, and also in the trachea mucosal layer of mutant mice compared with the control mice. Lack of lacteals in the intestinal villi and a marked decrease of lymphatics in the inner wall of colons were also observed in the Vegfr3lbd mutant mice. Consistently, lymphangiogenic sprouts were dramatically suppressed in the Vegfr3lbd mutant mice. Furthermore, we also observed some dilated lymphatic vessels in the dorsal skin and trachea of the heterozygous mice (Vegfr3lbd+/-, at P1), suggesting a dominant-negative effect of VEGFR3LBD. Induced deletion of the VEGFR3LBD at the juvenile stage (P16-21) led to a decrease of lymphatic vessel density in ear skin, while there was no obvious abnormality with lymphatic vessel formation detected in the diaphragm, trachea, and intestinal villi. Furthermore, the induced deletion of the VEGFR3LBD did not produce obvious lymphatic phenotype in several tissue examined at the adult stage (2 month-old). However, there was some dilated lymphatic vessels detected in the diaphragm and skin of the Vegfr3lbd mutant mice. Conclusion: In summary, findings from this study indicate that the VEGFR3LBD-mediated signaling is essential for lymphangiogenesis at the neonatal stage, but is less required for the lymphatic vessel growth and maintenance from the juvenile stage onwards. It is worth noting that the dilation of lymphatic vessels observed in some Vegfr3lbd mutant mice at the adult stage may be related to the developmental lymphatic defects resulting from the dominant-negative effect of VEGFR3LBD.

Keywords： Vascular Endothelial Growth Factor Receptor-3 (VEGFR3) VEGFR3 Ligand-Binding Domain (LBD) Lymphangiogenesis Lymphatic Homeostasis Conditional Knockout Mouse