生物
淋巴管新生
真皮
福克斯O1
细胞生物学
表皮(动物学)
癌症研究
蛋白激酶B
解剖
CXCR4型
免疫学
信号转导
遗传学
趋化因子
癌症
转移
炎症
作者
Kenta Niimi,Misaki Kohara,Eriko Sedoh,Moe Fukumoto,Satoshi Shibata,Toshinori Sawano,Fumi Tashiro,Satsuki Miyazaki,Yoshiaki Kubota,Jun Miyazaki,Shinobu Inagaki,Tatsuo Furuyama
出处
期刊:Development
[The Company of Biologists]
日期:2019-01-01
被引量:16
摘要
Lymphangiogenesis plays important roles in normal fetal development and postnatal growth. However, its molecular regulation remains unclear. Here, we have examined the function of forkhead box protein O1 (FOXO1) transcription factor, a known angiogenic factor, in developmental dermal lymphangiogenesis using endothelial cell-specific FOXO1-deficient mice. FOXO1-deficient mice showed disconnected and dilated lymphatic vessels accompanied with increased proliferation and decreased apoptosis in the lymphatic capillaries. Comprehensive DNA microarray analysis of the causes of in vivo phenotypes in FOXO1-deficient mice revealed that the gene encoding C-X-C chemokine receptor 4 (CXCR4) was the most drastically downregulated in FOXO1-deficient primary lymphatic endothelial cells (LECs). CXCR4 was expressed in developing dermal lymphatic capillaries in wild-type mice but not in FOXO1-deficient dermal lymphatic capillaries. Furthermore, FOXO1 suppression impaired migration toward the exogenous CXCR4 ligand, C-X-C chemokine ligand 12 (CXCL12), and coordinated proliferation in LECs. These results suggest that FOXO1 serves an essential role in normal developmental lymphangiogenesis by promoting LEC migration toward CXCL12 and by regulating their proliferative activity. This study provides valuable insights into the molecular mechanisms underlying developmental lymphangiogenesis.
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