Angiopoietin 2 regulates the transformation and integrity of lymphatic endothelial cell junctions.

Details

Serval ID
serval:BIB_6DA335ABEBDB
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Angiopoietin 2 regulates the transformation and integrity of lymphatic endothelial cell junctions.
Journal
Genes and Development
Author(s)
Zheng W., Nurmi H., Appak S., Sabine A., Bovay E., Korhonen E.A., Orsenigo F., Lohela M., D'Amico G., Holopainen T., Leow C.C., Dejana E., Petrova T.V., Augustin H.G., Alitalo K.
ISSN
1549-5477 (Electronic)
ISSN-L
0890-9369
Publication state
Published
Issued date
2014
Volume
28
Number
14
Pages
1592-1603
Language
english
Abstract
Primitive lymphatic vessels are remodeled into functionally specialized initial and collecting lymphatics during development. Lymphatic endothelial cell (LEC) junctions in initial lymphatics transform from a zipper-like to a button-like pattern during collecting vessel development, but what regulates this process is largely unknown. Angiopoietin 2 (Ang2) deficiency leads to abnormal lymphatic vessels. Here we found that an ANG2-blocking antibody inhibited embryonic lymphangiogenesis, whereas endothelium-specific ANG2 overexpression induced lymphatic hyperplasia. ANG2 inhibition blocked VE-cadherin phosphorylation at tyrosine residue 685 and the concomitant formation of button-like junctions in initial lymphatics. The defective junctions were associated with impaired lymph uptake. In collecting lymphatics, adherens junctions were disrupted, and the vessels leaked upon ANG2 blockade or gene deletion. ANG2 inhibition also suppressed the onset of lymphatic valve formation and subsequent valve maturation. These data identify ANG2 as the first essential regulator of the functionally important interendothelial cell-cell junctions that form during lymphatic development.
Keywords
Angiopoietin-2/antagonists & inhibitors, Angiopoietin-2/genetics, Animals, Cadherins/metabolism, Embryo, Mammalian, Endothelial Cells/cytology, Endothelial Cells/metabolism, Gene Deletion, Intercellular Junctions/physiology, Lymphangiogenesis/physiology, Lymphoid Tissue/embryology, Lymphoid Tissue/pathology, Mice, Mice, Inbred C57BL, Phosphorylation
Pubmed
Web of science
Open Access
Yes
Create date
16/01/2015 16:03
Last modification date
20/08/2019 15:27
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