Cargando…
Polydom/SVEP1 binds to Tie1 and promotes migration of lymphatic endothelial cells
Polydom is an extracellular matrix protein involved in lymphatic vessel development. Polydom-deficient mice die immediately after birth due to defects in lymphatic vessel remodeling, but the mechanism involved is poorly understood. Here, we report that Polydom directly binds to Tie1, an orphan recep...
Autores principales: | , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Rockefeller University Press
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10281526/ https://www.ncbi.nlm.nih.gov/pubmed/37338522 http://dx.doi.org/10.1083/jcb.202208047 |
_version_ | 1785061021325459456 |
---|---|
author | Sato-Nishiuchi, Ryoko Doiguchi, Masamichi Morooka, Nanami Sekiguchi, Kiyotoshi |
author_facet | Sato-Nishiuchi, Ryoko Doiguchi, Masamichi Morooka, Nanami Sekiguchi, Kiyotoshi |
author_sort | Sato-Nishiuchi, Ryoko |
collection | PubMed |
description | Polydom is an extracellular matrix protein involved in lymphatic vessel development. Polydom-deficient mice die immediately after birth due to defects in lymphatic vessel remodeling, but the mechanism involved is poorly understood. Here, we report that Polydom directly binds to Tie1, an orphan receptor in the Angiopoietin–Tie axis, and facilitates migration of lymphatic endothelial cells (LECs) in a Tie1-dependent manner. Polydom-induced LEC migration is diminished by PI3K inhibitors but not by an ERK inhibitor, suggesting that the PI3K/Akt signaling pathway is involved in Polydom-induced LEC migration. In line with this possibility, Akt phosphorylation in LECs is enhanced by Polydom although no significant Tie1 phosphorylation is induced by Polydom. LECs also exhibited nuclear exclusion of Foxo1, a signaling event downstream of Akt activation, which was impaired in Polydom-deficient mice. These findings indicate that Polydom is a physiological ligand for Tie1 and participates in lymphatic vessel development through activation of the PI3K/Akt pathway. |
format | Online Article Text |
id | pubmed-10281526 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-102815262023-06-21 Polydom/SVEP1 binds to Tie1 and promotes migration of lymphatic endothelial cells Sato-Nishiuchi, Ryoko Doiguchi, Masamichi Morooka, Nanami Sekiguchi, Kiyotoshi J Cell Biol Article Polydom is an extracellular matrix protein involved in lymphatic vessel development. Polydom-deficient mice die immediately after birth due to defects in lymphatic vessel remodeling, but the mechanism involved is poorly understood. Here, we report that Polydom directly binds to Tie1, an orphan receptor in the Angiopoietin–Tie axis, and facilitates migration of lymphatic endothelial cells (LECs) in a Tie1-dependent manner. Polydom-induced LEC migration is diminished by PI3K inhibitors but not by an ERK inhibitor, suggesting that the PI3K/Akt signaling pathway is involved in Polydom-induced LEC migration. In line with this possibility, Akt phosphorylation in LECs is enhanced by Polydom although no significant Tie1 phosphorylation is induced by Polydom. LECs also exhibited nuclear exclusion of Foxo1, a signaling event downstream of Akt activation, which was impaired in Polydom-deficient mice. These findings indicate that Polydom is a physiological ligand for Tie1 and participates in lymphatic vessel development through activation of the PI3K/Akt pathway. Rockefeller University Press 2023-06-20 /pmc/articles/PMC10281526/ /pubmed/37338522 http://dx.doi.org/10.1083/jcb.202208047 Text en © 2023 Sato-Nishiuchi et al. https://creativecommons.org/licenses/by/4.0/This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Sato-Nishiuchi, Ryoko Doiguchi, Masamichi Morooka, Nanami Sekiguchi, Kiyotoshi Polydom/SVEP1 binds to Tie1 and promotes migration of lymphatic endothelial cells |
title | Polydom/SVEP1 binds to Tie1 and promotes migration of lymphatic endothelial cells |
title_full | Polydom/SVEP1 binds to Tie1 and promotes migration of lymphatic endothelial cells |
title_fullStr | Polydom/SVEP1 binds to Tie1 and promotes migration of lymphatic endothelial cells |
title_full_unstemmed | Polydom/SVEP1 binds to Tie1 and promotes migration of lymphatic endothelial cells |
title_short | Polydom/SVEP1 binds to Tie1 and promotes migration of lymphatic endothelial cells |
title_sort | polydom/svep1 binds to tie1 and promotes migration of lymphatic endothelial cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10281526/ https://www.ncbi.nlm.nih.gov/pubmed/37338522 http://dx.doi.org/10.1083/jcb.202208047 |
work_keys_str_mv | AT satonishiuchiryoko polydomsvep1bindstotie1andpromotesmigrationoflymphaticendothelialcells AT doiguchimasamichi polydomsvep1bindstotie1andpromotesmigrationoflymphaticendothelialcells AT morookananami polydomsvep1bindstotie1andpromotesmigrationoflymphaticendothelialcells AT sekiguchikiyotoshi polydomsvep1bindstotie1andpromotesmigrationoflymphaticendothelialcells |