LPA4 regulates blood and lymphatic vessel formation during mouse embryogenesis

Hayakazu Sumida, Kyoko Noguchi, Yasuyuki Kihara, Manabu Abe, Keisuke Yanagida, Fumie Hamano, Shinichi Sato, Kunihiko Tamaki, Yasuyuki Morishita, Mitsunobu Kano, Caname Iwata, Kohei Miyazono, Kenji Sakimura, Takao Shimizu, Satoshi Ishii

Research output: Contribution to journalArticle

80 Citations (Scopus)

Abstract

Lysophosphatidic acid (LPA) is a potent lipid mediator with a wide variety of biological actions mediated through G protein-coupled receptors (LPA 1-6). LPA4 has been identified as a G13 protein-coupled receptor, but its physiological role is unknown. Here we show that a subset of LPA4-deficient embryos did not survive gestation and displayed hemorrhages and/or edema in many organs at multiple embryonic stages. The blood vessels of bleeding LPA4-deficient embryos were often dilated. The recruitment of mural cells, namely smooth muscle cells and pericytes, was impaired. Consistently, Matrigel plug assays showed decreased mural cell coverage of endothelial cells in the neovessels of LPA 4-deficient adult mice. In situ hybridization detected Lpa4 mRNA in the endothelium of some vasculatures. Similarly, the lymphatic vessels of edematous embryos were dilated. These results suggest that LPA4 regulates establishment of the structure and function of blood and lymphatic vessels during mouse embryogenesis. Considering the critical role of autotaxin (an enzyme involved in LPA production) and Gα13 in vascular development, we suggest that LPA4 provides a link between these 2 molecules.

Original languageEnglish
Pages (from-to)5060-5070
Number of pages11
JournalBlood
Volume116
Issue number23
DOIs
Publication statusPublished - Dec 2 2010
Externally publishedYes

Fingerprint

Lymphatic Vessels
Embryonic Development
Blood Vessels
Blood
Embryonic Structures
G12-G13 GTP-Binding Protein alpha Subunits
Hemorrhage
Pericytes
Endothelial cells
Blood vessels
G-Protein-Coupled Receptors
Smooth Muscle Myocytes
Endothelium
In Situ Hybridization
Muscle
Assays
Edema
Endothelial Cells
Cells
Lipids

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Sumida, H., Noguchi, K., Kihara, Y., Abe, M., Yanagida, K., Hamano, F., ... Ishii, S. (2010). LPA4 regulates blood and lymphatic vessel formation during mouse embryogenesis. Blood, 116(23), 5060-5070. https://doi.org/10.1182/blood-2010-03-272443

LPA4 regulates blood and lymphatic vessel formation during mouse embryogenesis. / Sumida, Hayakazu; Noguchi, Kyoko; Kihara, Yasuyuki; Abe, Manabu; Yanagida, Keisuke; Hamano, Fumie; Sato, Shinichi; Tamaki, Kunihiko; Morishita, Yasuyuki; Kano, Mitsunobu; Iwata, Caname; Miyazono, Kohei; Sakimura, Kenji; Shimizu, Takao; Ishii, Satoshi.

In: Blood, Vol. 116, No. 23, 02.12.2010, p. 5060-5070.

Research output: Contribution to journalArticle

Sumida, H, Noguchi, K, Kihara, Y, Abe, M, Yanagida, K, Hamano, F, Sato, S, Tamaki, K, Morishita, Y, Kano, M, Iwata, C, Miyazono, K, Sakimura, K, Shimizu, T & Ishii, S 2010, 'LPA4 regulates blood and lymphatic vessel formation during mouse embryogenesis', Blood, vol. 116, no. 23, pp. 5060-5070. https://doi.org/10.1182/blood-2010-03-272443
Sumida H, Noguchi K, Kihara Y, Abe M, Yanagida K, Hamano F et al. LPA4 regulates blood and lymphatic vessel formation during mouse embryogenesis. Blood. 2010 Dec 2;116(23):5060-5070. https://doi.org/10.1182/blood-2010-03-272443
Sumida, Hayakazu ; Noguchi, Kyoko ; Kihara, Yasuyuki ; Abe, Manabu ; Yanagida, Keisuke ; Hamano, Fumie ; Sato, Shinichi ; Tamaki, Kunihiko ; Morishita, Yasuyuki ; Kano, Mitsunobu ; Iwata, Caname ; Miyazono, Kohei ; Sakimura, Kenji ; Shimizu, Takao ; Ishii, Satoshi. / LPA4 regulates blood and lymphatic vessel formation during mouse embryogenesis. In: Blood. 2010 ; Vol. 116, No. 23. pp. 5060-5070.
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AU - Sato, Shinichi

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