CD146 is required for VEGF-C-induced lymphatic sprouting during lymphangiogenesis

Abstract VEGF-C is essential for lymphangiogenesis during development and tumor progression. VEGFR-3 is the well-known cognate receptor of VEGF-C to regulate lymphatic migration and proliferation, but the receptor of VEGF-C in regulating lymphatic sprouting, the initiating step of lymphangiogenesis,...

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Autores principales: Huiwen Yan, Chunxia Zhang, Zhaoqing Wang, Tao Tu, Hongxia Duan, Yongting Luo, Jing Feng, Feng Liu, Xiyun Yan
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Lenguaje:EN
Publicado: Nature Portfolio 2017
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Acceso en línea:https://doaj.org/article/4d1e441c3f244756937f4c70036fe27c
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spelling oai:doaj.org-article:4d1e441c3f244756937f4c70036fe27c2021-12-02T12:31:51ZCD146 is required for VEGF-C-induced lymphatic sprouting during lymphangiogenesis10.1038/s41598-017-06637-72045-2322https://doaj.org/article/4d1e441c3f244756937f4c70036fe27c2017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-06637-7https://doaj.org/toc/2045-2322Abstract VEGF-C is essential for lymphangiogenesis during development and tumor progression. VEGFR-3 is the well-known cognate receptor of VEGF-C to regulate lymphatic migration and proliferation, but the receptor of VEGF-C in regulating lymphatic sprouting, the initiating step of lymphangiogenesis, still remains elusive. Here we use both in vitro and in vivo methods to demonstrate CD146 as a receptor of VEGF-C to regulate lymphangiogenesis, especially at the sprouting step. Mechanistically, CD146 selectively activates the downstream p38 kinase, upon VEGF-C stimulation, to regulate lymphatic sprouting. Moreover, CD146 can also activate ERK to mediate VEGF-C regulation of the subsequent proliferation and migration of lymphatic endothelial cells. In zebrafish embryos, knockdown or dysfunction of CD146 results in similar developmental defects in lymphatic sprouting, capillary network, parachordal lymphangioblast (PL), and thoracic duct (TD) similar to down-regulation of VEGF-C. Altogether, our data reveals a critical role of CD146 to mediate VEGF-C signaling pathway in lymphangiogenesis.Huiwen YanChunxia ZhangZhaoqing WangTao TuHongxia DuanYongting LuoJing FengFeng LiuXiyun YanNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Huiwen Yan
Chunxia Zhang
Zhaoqing Wang
Tao Tu
Hongxia Duan
Yongting Luo
Jing Feng
Feng Liu
Xiyun Yan
CD146 is required for VEGF-C-induced lymphatic sprouting during lymphangiogenesis
description Abstract VEGF-C is essential for lymphangiogenesis during development and tumor progression. VEGFR-3 is the well-known cognate receptor of VEGF-C to regulate lymphatic migration and proliferation, but the receptor of VEGF-C in regulating lymphatic sprouting, the initiating step of lymphangiogenesis, still remains elusive. Here we use both in vitro and in vivo methods to demonstrate CD146 as a receptor of VEGF-C to regulate lymphangiogenesis, especially at the sprouting step. Mechanistically, CD146 selectively activates the downstream p38 kinase, upon VEGF-C stimulation, to regulate lymphatic sprouting. Moreover, CD146 can also activate ERK to mediate VEGF-C regulation of the subsequent proliferation and migration of lymphatic endothelial cells. In zebrafish embryos, knockdown or dysfunction of CD146 results in similar developmental defects in lymphatic sprouting, capillary network, parachordal lymphangioblast (PL), and thoracic duct (TD) similar to down-regulation of VEGF-C. Altogether, our data reveals a critical role of CD146 to mediate VEGF-C signaling pathway in lymphangiogenesis.
format article
author Huiwen Yan
Chunxia Zhang
Zhaoqing Wang
Tao Tu
Hongxia Duan
Yongting Luo
Jing Feng
Feng Liu
Xiyun Yan
author_facet Huiwen Yan
Chunxia Zhang
Zhaoqing Wang
Tao Tu
Hongxia Duan
Yongting Luo
Jing Feng
Feng Liu
Xiyun Yan
author_sort Huiwen Yan
title CD146 is required for VEGF-C-induced lymphatic sprouting during lymphangiogenesis
title_short CD146 is required for VEGF-C-induced lymphatic sprouting during lymphangiogenesis
title_full CD146 is required for VEGF-C-induced lymphatic sprouting during lymphangiogenesis
title_fullStr CD146 is required for VEGF-C-induced lymphatic sprouting during lymphangiogenesis
title_full_unstemmed CD146 is required for VEGF-C-induced lymphatic sprouting during lymphangiogenesis
title_sort cd146 is required for vegf-c-induced lymphatic sprouting during lymphangiogenesis
publisher Nature Portfolio
publishDate 2017
url https://doaj.org/article/4d1e441c3f244756937f4c70036fe27c
work_keys_str_mv AT huiwenyan cd146isrequiredforvegfcinducedlymphaticsproutingduringlymphangiogenesis
AT chunxiazhang cd146isrequiredforvegfcinducedlymphaticsproutingduringlymphangiogenesis
AT zhaoqingwang cd146isrequiredforvegfcinducedlymphaticsproutingduringlymphangiogenesis
AT taotu cd146isrequiredforvegfcinducedlymphaticsproutingduringlymphangiogenesis
AT hongxiaduan cd146isrequiredforvegfcinducedlymphaticsproutingduringlymphangiogenesis
AT yongtingluo cd146isrequiredforvegfcinducedlymphaticsproutingduringlymphangiogenesis
AT jingfeng cd146isrequiredforvegfcinducedlymphaticsproutingduringlymphangiogenesis
AT fengliu cd146isrequiredforvegfcinducedlymphaticsproutingduringlymphangiogenesis
AT xiyunyan cd146isrequiredforvegfcinducedlymphaticsproutingduringlymphangiogenesis
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