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 R. Kano, Caname Iwata, Kohei Miyazono, Kenji Sakimura, Takao Shimizu, Satoshi Ishii

Research output: Contribution to journalArticlepeer-review

103 Citations (Scopus)


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
Issue number23
Publication statusPublished - Dec 2 2010
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology


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