Essential role of prostaglandin E2 and the EP3 receptor in lymphatic vessel development during zebrafish embryogenesis

Abstract Lymphatic endothelial cells arise from the venous endothelial cells in embryonic lymphatic development. However, the molecular mechanisms remain to be elucidated. We here report that prostaglandin (PG) E2 plays essential roles in the embryonic lymphatic development through the EP3 receptor,...

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Autores principales:	Ryo Iwasaki, Kyoshiro Tsuge, Koichiro Kishimoto, Yuta Hayashi, Takuya Iwaana, Hirofumi Hohjoh, Tomoaki Inazumi, Atsuo Kawahara, Soken Tsuchiya, Yukihiko Sugimoto
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2019
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b4f00d0dbb1c4106b21bf77585765da8
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spelling	oai:doaj.org-article:b4f00d0dbb1c4106b21bf77585765da82021-12-02T15:09:52ZEssential role of prostaglandin E2 and the EP3 receptor in lymphatic vessel development during zebrafish embryogenesis10.1038/s41598-019-44095-52045-2322https://doaj.org/article/b4f00d0dbb1c4106b21bf77585765da82019-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-44095-5https://doaj.org/toc/2045-2322Abstract Lymphatic endothelial cells arise from the venous endothelial cells in embryonic lymphatic development. However, the molecular mechanisms remain to be elucidated. We here report that prostaglandin (PG) E2 plays essential roles in the embryonic lymphatic development through the EP3 receptor, one of the PGE2 receptors. Knockdown of the EP3 receptor or inhibition of cyclooxygenases (COX; rate-limiting enzymes for PG synthesis) impaired lymphatic development by perturbing lymphatic specification during zebrafish development. These impairments by COX inhibition were recovered by treatment with sulprostone (EP1/3 agonist). Knockdown of the EP3 receptor further demonstrated its requirement in the expression of sex determining region Y-box 18 (sox18) and nuclear receptor subfamily 2, group F, member 2 (nr2f2), essential factors of the lymphatic specification. The EP3 receptor was expressed in the posterior cardinal vein (region of embryonic lymphatic development) and the adjacent intermediate cell mass (ICM) during the lymphatic specification. COX1 was expressed in the region more upstream of the posterior cardinal vein relative to the EP3 receptor, and the COX1-selective inhibitor impaired the lymphatic specification. On the other hand, two COX2 subtypes did not show distinct sites of expression around the region of expression of the EP3 receptor. Finally, we generated EP3-deficient zebrafish, which also showed defect in lymphatic specification and development. Thus, we demonstrated that COX1-derived PGE2-EP3 pathway is required for embryonic lymphatic development by upregulating the expression of key factors for the lymphatic specification.Ryo IwasakiKyoshiro TsugeKoichiro KishimotoYuta HayashiTakuya IwaanaHirofumi HohjohTomoaki InazumiAtsuo KawaharaSoken TsuchiyaYukihiko SugimotoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-11 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ryo Iwasaki Kyoshiro Tsuge Koichiro Kishimoto Yuta Hayashi Takuya Iwaana Hirofumi Hohjoh Tomoaki Inazumi Atsuo Kawahara Soken Tsuchiya Yukihiko Sugimoto Essential role of prostaglandin E2 and the EP3 receptor in lymphatic vessel development during zebrafish embryogenesis
description	Abstract Lymphatic endothelial cells arise from the venous endothelial cells in embryonic lymphatic development. However, the molecular mechanisms remain to be elucidated. We here report that prostaglandin (PG) E2 plays essential roles in the embryonic lymphatic development through the EP3 receptor, one of the PGE2 receptors. Knockdown of the EP3 receptor or inhibition of cyclooxygenases (COX; rate-limiting enzymes for PG synthesis) impaired lymphatic development by perturbing lymphatic specification during zebrafish development. These impairments by COX inhibition were recovered by treatment with sulprostone (EP1/3 agonist). Knockdown of the EP3 receptor further demonstrated its requirement in the expression of sex determining region Y-box 18 (sox18) and nuclear receptor subfamily 2, group F, member 2 (nr2f2), essential factors of the lymphatic specification. The EP3 receptor was expressed in the posterior cardinal vein (region of embryonic lymphatic development) and the adjacent intermediate cell mass (ICM) during the lymphatic specification. COX1 was expressed in the region more upstream of the posterior cardinal vein relative to the EP3 receptor, and the COX1-selective inhibitor impaired the lymphatic specification. On the other hand, two COX2 subtypes did not show distinct sites of expression around the region of expression of the EP3 receptor. Finally, we generated EP3-deficient zebrafish, which also showed defect in lymphatic specification and development. Thus, we demonstrated that COX1-derived PGE2-EP3 pathway is required for embryonic lymphatic development by upregulating the expression of key factors for the lymphatic specification.
format	article
author	Ryo Iwasaki Kyoshiro Tsuge Koichiro Kishimoto Yuta Hayashi Takuya Iwaana Hirofumi Hohjoh Tomoaki Inazumi Atsuo Kawahara Soken Tsuchiya Yukihiko Sugimoto
author_facet	Ryo Iwasaki Kyoshiro Tsuge Koichiro Kishimoto Yuta Hayashi Takuya Iwaana Hirofumi Hohjoh Tomoaki Inazumi Atsuo Kawahara Soken Tsuchiya Yukihiko Sugimoto
author_sort	Ryo Iwasaki
title	Essential role of prostaglandin E2 and the EP3 receptor in lymphatic vessel development during zebrafish embryogenesis
title_short	Essential role of prostaglandin E2 and the EP3 receptor in lymphatic vessel development during zebrafish embryogenesis
title_full	Essential role of prostaglandin E2 and the EP3 receptor in lymphatic vessel development during zebrafish embryogenesis
title_fullStr	Essential role of prostaglandin E2 and the EP3 receptor in lymphatic vessel development during zebrafish embryogenesis
title_full_unstemmed	Essential role of prostaglandin E2 and the EP3 receptor in lymphatic vessel development during zebrafish embryogenesis
title_sort	essential role of prostaglandin e2 and the ep3 receptor in lymphatic vessel development during zebrafish embryogenesis
publisher	Nature Portfolio
publishDate	2019
url	https://doaj.org/article/b4f00d0dbb1c4106b21bf77585765da8
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Essential role of prostaglandin E2 and the EP3 receptor in lymphatic vessel development during zebrafish embryogenesis

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