Isolation and characterisation of lymphatic endothelial cells from lung tissues affected by lymphangioleiomyomatosis

Abstract Lymphangioleiomyomatosis (LAM) is a rare pulmonary disease characterised by the proliferation of smooth muscle-like cells (LAM cells), and an abundance of lymphatic vessels in LAM lesions. Studies reported that vascular endothelial growth factor-D (VEGF-D) secreted by LAM cells contributes...

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Autores principales:	Koichi Nishino, Yasuhiro Yoshimatsu, Tomoki Muramatsu, Yasuhito Sekimoto, Keiko Mitani, Etsuko Kobayashi, Shouichi Okamoto, Hiroki Ebana, Yoshinori Okada, Masatoshi Kurihara, Kenji Suzuki, Johji Inazawa, Kazuhisa Takahashi, Tetsuro Watabe, Kuniaki Seyama
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2ab2d6be5e714483911e6f086b4389fc
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spelling	oai:doaj.org-article:2ab2d6be5e714483911e6f086b4389fc2021-12-02T14:26:20ZIsolation and characterisation of lymphatic endothelial cells from lung tissues affected by lymphangioleiomyomatosis10.1038/s41598-021-88064-32045-2322https://doaj.org/article/2ab2d6be5e714483911e6f086b4389fc2021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-88064-3https://doaj.org/toc/2045-2322Abstract Lymphangioleiomyomatosis (LAM) is a rare pulmonary disease characterised by the proliferation of smooth muscle-like cells (LAM cells), and an abundance of lymphatic vessels in LAM lesions. Studies reported that vascular endothelial growth factor-D (VEGF-D) secreted by LAM cells contributes to LAM-associated lymphangiogenesis, however, the precise mechanisms of lymphangiogenesis and characteristics of lymphatic endothelial cells (LECs) in LAM lesions have not yet been elucidated. In this study, human primary-cultured LECs were obtained both from LAM-affected lung tissues (LAM-LECs) and normal lung tissues (control LECs) using fluorescence-activated cell sorting (FACS). We found that LAM-LECs had significantly higher ability of proliferation and migration compared to control LECs. VEGF-D significantly promoted migration of LECs but not proliferation of LECs in vitro. cDNA microarray and FACS analysis revealed the expression of vascular endothelial growth factor receptor (VEGFR)-3 and integrin α9 were elevated in LAM-LECs. Inhibition of VEGFR-3 suppressed proliferation and migration of LECs, and blockade of integrin α9 reduced VEGF-D-induced migration of LECs. Our data uncovered the distinct features of LAM-associated LECs, increased proliferation and migration, which may be due to higher expression of VEGFR-3 and integrin α9. Furthermore, we also found VEGF-D/VEGFR-3 and VEGF-D/ integrin α9 signaling play an important role in LAM-associated lymphangiogenesis.Koichi NishinoYasuhiro YoshimatsuTomoki MuramatsuYasuhito SekimotoKeiko MitaniEtsuko KobayashiShouichi OkamotoHiroki EbanaYoshinori OkadaMasatoshi KuriharaKenji SuzukiJohji InazawaKazuhisa TakahashiTetsuro WatabeKuniaki SeyamaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Koichi Nishino Yasuhiro Yoshimatsu Tomoki Muramatsu Yasuhito Sekimoto Keiko Mitani Etsuko Kobayashi Shouichi Okamoto Hiroki Ebana Yoshinori Okada Masatoshi Kurihara Kenji Suzuki Johji Inazawa Kazuhisa Takahashi Tetsuro Watabe Kuniaki Seyama Isolation and characterisation of lymphatic endothelial cells from lung tissues affected by lymphangioleiomyomatosis
description	Abstract Lymphangioleiomyomatosis (LAM) is a rare pulmonary disease characterised by the proliferation of smooth muscle-like cells (LAM cells), and an abundance of lymphatic vessels in LAM lesions. Studies reported that vascular endothelial growth factor-D (VEGF-D) secreted by LAM cells contributes to LAM-associated lymphangiogenesis, however, the precise mechanisms of lymphangiogenesis and characteristics of lymphatic endothelial cells (LECs) in LAM lesions have not yet been elucidated. In this study, human primary-cultured LECs were obtained both from LAM-affected lung tissues (LAM-LECs) and normal lung tissues (control LECs) using fluorescence-activated cell sorting (FACS). We found that LAM-LECs had significantly higher ability of proliferation and migration compared to control LECs. VEGF-D significantly promoted migration of LECs but not proliferation of LECs in vitro. cDNA microarray and FACS analysis revealed the expression of vascular endothelial growth factor receptor (VEGFR)-3 and integrin α9 were elevated in LAM-LECs. Inhibition of VEGFR-3 suppressed proliferation and migration of LECs, and blockade of integrin α9 reduced VEGF-D-induced migration of LECs. Our data uncovered the distinct features of LAM-associated LECs, increased proliferation and migration, which may be due to higher expression of VEGFR-3 and integrin α9. Furthermore, we also found VEGF-D/VEGFR-3 and VEGF-D/ integrin α9 signaling play an important role in LAM-associated lymphangiogenesis.
format	article
author	Koichi Nishino Yasuhiro Yoshimatsu Tomoki Muramatsu Yasuhito Sekimoto Keiko Mitani Etsuko Kobayashi Shouichi Okamoto Hiroki Ebana Yoshinori Okada Masatoshi Kurihara Kenji Suzuki Johji Inazawa Kazuhisa Takahashi Tetsuro Watabe Kuniaki Seyama
author_facet	Koichi Nishino Yasuhiro Yoshimatsu Tomoki Muramatsu Yasuhito Sekimoto Keiko Mitani Etsuko Kobayashi Shouichi Okamoto Hiroki Ebana Yoshinori Okada Masatoshi Kurihara Kenji Suzuki Johji Inazawa Kazuhisa Takahashi Tetsuro Watabe Kuniaki Seyama
author_sort	Koichi Nishino
title	Isolation and characterisation of lymphatic endothelial cells from lung tissues affected by lymphangioleiomyomatosis
title_short	Isolation and characterisation of lymphatic endothelial cells from lung tissues affected by lymphangioleiomyomatosis
title_full	Isolation and characterisation of lymphatic endothelial cells from lung tissues affected by lymphangioleiomyomatosis
title_fullStr	Isolation and characterisation of lymphatic endothelial cells from lung tissues affected by lymphangioleiomyomatosis
title_full_unstemmed	Isolation and characterisation of lymphatic endothelial cells from lung tissues affected by lymphangioleiomyomatosis
title_sort	isolation and characterisation of lymphatic endothelial cells from lung tissues affected by lymphangioleiomyomatosis
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/2ab2d6be5e714483911e6f086b4389fc
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Isolation and characterisation of lymphatic endothelial cells from lung tissues affected by lymphangioleiomyomatosis

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