| http://purl.uniprot.org/citations/17210781 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/17210781 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/17210781 | http://www.w3.org/2000/01/rdf-schema#comment | "Activation of vascular endothelial growth factor (VEGF) receptor-3 (VEGFR-3) by VEGF-C initiates lymphangiogenesis by promoting lymphatic proliferation and migration. However, it is unclear whether VEGFR-3 signaling is required beyond these initial stages, namely during the organization of new lymphatic endothelial cells (LECs) into functional capillaries. Furthermore, the role of VEGFR-2, which is also expressed on LECs and binds VEGF-C, is unclear. We addressed these questions by selectively neutralizing VEGFR-3 and/or VEGFR-2 for various time periods in an adult model of lymphangiogenesis in regenerating skin. While blocking either VEGFR-2 or VEGFR-3 with specific antagonist mAbs (DC101 and mF4-31C1, respectively) prior to lymphatic migration prevented lymphangiogenesis, blocking VEGFR-3 subsequent to migration did not affect organization into functional capillaries, and VEGFR-2 blocking had only a small hindrance on organization. These findings were confirmed in vitro using human LECs and anti-human antagonist mAbs (IMC-1121a and hF4-3C5): both VEGFR-2 and -3 signaling were required for migration and proliferation, but tubulogenesis in 3D cultures was unaffected by VEGFR-3 blocking and partially hindered by VEGFR-2 blocking. Furthermore, both in vitro and in vivo, while VEGFR-3 blocking had no effect on LEC organization, coneutralization of VEGFR-2, and VEGFR-3 completely prevented lymphatic organization. Our findings demonstrate that cooperative signaling of VEGFR-2 and -3 is necessary for lymphatic migration and proliferation, but VEGFR-3 is redundant with VEGFR-2 for LEC organization into functional capillaries."xsd:string |
| http://purl.uniprot.org/citations/17210781 | http://purl.org/dc/terms/identifier | "doi:10.1096/fj.06-6656com"xsd:string |
| http://purl.uniprot.org/citations/17210781 | http://purl.org/dc/terms/identifier | "doi:10.1096/fj.06-6656com"xsd:string |
| http://purl.uniprot.org/citations/17210781 | http://purl.uniprot.org/core/author | "Cui Y."xsd:string |
| http://purl.uniprot.org/citations/17210781 | http://purl.uniprot.org/core/author | "Cui Y."xsd:string |
| http://purl.uniprot.org/citations/17210781 | http://purl.uniprot.org/core/author | "Goldman J."xsd:string |
| http://purl.uniprot.org/citations/17210781 | http://purl.uniprot.org/core/author | "Goldman J."xsd:string |
| http://purl.uniprot.org/citations/17210781 | http://purl.uniprot.org/core/author | "Willey S."xsd:string |
| http://purl.uniprot.org/citations/17210781 | http://purl.uniprot.org/core/author | "Willey S."xsd:string |
| http://purl.uniprot.org/citations/17210781 | http://purl.uniprot.org/core/author | "Hicklin D.J."xsd:string |
| http://purl.uniprot.org/citations/17210781 | http://purl.uniprot.org/core/author | "Hicklin D.J."xsd:string |
| http://purl.uniprot.org/citations/17210781 | http://purl.uniprot.org/core/author | "Pytowski B."xsd:string |
| http://purl.uniprot.org/citations/17210781 | http://purl.uniprot.org/core/author | "Pytowski B."xsd:string |
| http://purl.uniprot.org/citations/17210781 | http://purl.uniprot.org/core/author | "Pasquier M.C."xsd:string |
| http://purl.uniprot.org/citations/17210781 | http://purl.uniprot.org/core/author | "Pasquier M.C."xsd:string |
| http://purl.uniprot.org/citations/17210781 | http://purl.uniprot.org/core/author | "Rutkowski J.M."xsd:string |
| http://purl.uniprot.org/citations/17210781 | http://purl.uniprot.org/core/author | "Rutkowski J.M."xsd:string |
| http://purl.uniprot.org/citations/17210781 | http://purl.uniprot.org/core/author | "Schmokel H.G."xsd:string |
| http://purl.uniprot.org/citations/17210781 | http://purl.uniprot.org/core/author | "Schmokel H.G."xsd:string |
| http://purl.uniprot.org/citations/17210781 | http://purl.uniprot.org/core/author | "Shields J.D."xsd:string |
| http://purl.uniprot.org/citations/17210781 | http://purl.uniprot.org/core/author | "Shields J.D."xsd:string |
| http://purl.uniprot.org/citations/17210781 | http://purl.uniprot.org/core/author | "Swartz M.A."xsd:string |
| http://purl.uniprot.org/citations/17210781 | http://purl.uniprot.org/core/author | "Swartz M.A."xsd:string |