Novel zebrafish model reveals a critical role for MAPK in lymphangiogenesis.
Novel zebrafish model reveals a critical role for MAPK in lymphangiogenesis.
复制标题
DOI：
10.1016/j.jpedsurg.2011.10.035
复制
发表时间：
2012-01
影响因子：
2.4
通讯作者：
Chan J
中科院分区：
文献类型：
--
作者：
Fevurly RD;Hasso S;Fye A;Fishman SJ;Chan J
Lymphatic disorders are poorly understood with few animal models. We designed a novel assay to measure lymphatic development using transgenic zebrafish with fluorescently labeled endothelial cells. Two major branches of the vascular endothelial growth factor receptor (VEGFR) signaling pathway were examined: the MAPK and PI3K pathways. Direct visualization of lymphatic development was performed in control embryos or under chemical inhibition. Treatment involved a 6-hour pulse of inhibitor at 3 days post fertilization (dpf). Fish were analyzed for the presence of the TD at 4 dpf (n > 100 specimens). TD formation was prevented using selective inhibitors against kinases (MAPK, PI3K/TOR, or VEGFR). These kinases were important for TD formation, as the lymphatic vessel failed to form in a majority of treated animals. Remarkably, MAPK pathway inhibition most robustly reduced lymphangiogenesis, demonstrated by a lack of lymphatic endothelial cells. We conclude that MAPK pathway function downstream of the VEGFRs is crucial at the early stages of TD development. This study provides a novel animal model and a potential target pathway for further investigation. We suggest further examination of MAPK pathway deregulation as a potential mechanism underlying lymphatic disease in humans.
登录
查看更多内容
DOI：
10.1016/j.pathophys.2009.10.004
发表时间：
2010-09-01
期刊：
Pathophysiology : the official journal of the International Society for Pathophysiology
影响因子：
--
作者：
Bahram, Fuad;Claesson-Welsh, Lena
通讯作者：
Claesson-Welsh, Lena
有效使用 PI3K 和 MEK 抑制剂治疗突变型 Kras G12D 和 PIK3CA H1047R 小鼠肺癌。
影响因子：
82.9
作者：
通讯作者：
--
影响因子：
10.5
作者：
Srinivasan, R. Sathish;Geng, Xin;Oliver, Guillermo
通讯作者：
Oliver, Guillermo
淋巴发育。
影响因子：
--
作者：
Butler, Matthew G.;Isogai, Sumio;Weinstein, Brant M.
通讯作者：
Weinstein, Brant M.
DOI：
10.1073/pnas.0712195105
发表时间：
2008-02-19
影响因子：
11.1
作者：
Bolcome, Robert E., III;Sullivan, Sarah E.;Chan, Joanne
通讯作者：
Chan, Joanne