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 language | English |
|---|---|
| Pages (from-to) | 5060-5070 |
| Number of pages | 11 |
| Journal | Blood |
| Volume | 116 |
| Issue number | 23 |
| DOIs | |
| Publication status | Published - Dec 2 2010 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Hematology
- Biochemistry
- Cell Biology
- Immunology
Cite this
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 journal › Article
}
TY - JOUR
T1 - LPA4 regulates blood and lymphatic vessel formation during mouse embryogenesis
AU - Sumida, Hayakazu
AU - Noguchi, Kyoko
AU - Kihara, Yasuyuki
AU - Abe, Manabu
AU - Yanagida, Keisuke
AU - Hamano, Fumie
AU - Sato, Shinichi
AU - Tamaki, Kunihiko
AU - Morishita, Yasuyuki
AU - Kano, Mitsunobu
AU - Iwata, Caname
AU - Miyazono, Kohei
AU - Sakimura, Kenji
AU - Shimizu, Takao
AU - Ishii, Satoshi
PY - 2010/12/2
Y1 - 2010/12/2
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=78649737050&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=78649737050&partnerID=8YFLogxK
U2 - 10.1182/blood-2010-03-272443
DO - 10.1182/blood-2010-03-272443
M3 - Article
C2 - 20713964
AN - SCOPUS:78649737050
VL - 116
SP - 5060
EP - 5070
JO - Blood
JF - Blood
SN - 0006-4971
IS - 23
ER -