Cooperative interaction of Angiopoietin-like proteins 1 and 2 in zebrafish vascular development.
Angiopoietin-like protein (Angptl) 1 and Angptl2, which are considered orphan ligands, are highly homologous, particularly in the fibrinogen-like domain containing the putative receptor binding site. This similarity suggests potentially cooperative functions between the two proteins. In this report, the function of Angptl1 and Angptl2 is analyzed by using morpholino antisense technology in zebrafish. Knockdown of both Angptl1 and Angptl2 produced severe vascular defects due to increased apoptosis of endothelial cells at the sprouting stage. In vitro studies showed that Angptl1 and Angptl2 have antiapoptotic activities through the phosphatidylinositol 3-kinase/Akt pathway, and coinjection of constitutively active Akt/protein kinase B mRNA rescued impaired vascular development seen in double knockdown embryos. These results provide a physiological demonstration of the cooperative interaction of Angptl1 and Angptl2 in endothelial cells through phosphatidylinositol 3-kinase/Akt mediated antiapoptotic activities.
Kubota
Yoshiaki
Y
Department of Cell Differentiation, The Sakaguchi Laboratory, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
Oike
Yuichi
Y
Satoh
Shinya
S
Tabata
Yoko
Y
Niikura
Yuichi
Y
Morisada
Tohru
T
Akao
Masaki
M
Urano
Takashi
T
Ito
Yasuhiro
Y
Miyamoto
Takeshi
T
Nagai
Norihiro
N
Koh
Gou Young
GY
Watanabe
Sumiko
S
Suda
Toshio
T
D000091304:Angiopoietin-Like Protein 1; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001808:Blood Vessels / Q000166:cytology / Q000196:embryology*; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D020868:Gene Silencing; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D020319:Oligodeoxyribonucleotides, Antisense / Q000008:administration & dosage / Q000235:genetics; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
D000091304:Angiopoietin-Like Protein 1; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins; D036341:Intercellular Signaling Peptides and Proteins; D020319:Oligodeoxyribonucleotides, Antisense; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D029961:Zebrafish Proteins; C504920:Angptl1 protein, zebrafish; C504921:angptl2b protein, zebrafish