| First Author | Horikami D | Year | 2023 |
| Journal | J Lipid Res | Volume | 64 |
| Issue | 10 | Pages | 100439 |
| PubMed ID | 37666361 | Mgi Jnum | J:343804 |
| Mgi Id | MGI:7542308 | Doi | 10.1016/j.jlr.2023.100439 |
| Citation | Horikami D, et al. (2023) Roles of lipocalin-type and hematopoietic prostaglandin D synthases in mouse retinal angiogenesis. J Lipid Res 64(10):100439 |
| abstractText | Normal angiogenesis is essential for retinal development and maintenance of visual function in the eye, and its abnormality can cause retinopathy and other eye diseases. Prostaglandin D(2) is an anti-angiogenic lipid mediator produced by lipocalin-type PGD synthase (L-PGDS) or hematopoietic PGD synthase (H-PGDS). However, the exact role of these PGD synthases remains unclear. Therefore, we compared the roles of these synthases in murine retinal angiogenesis under physiological and pathological conditions. On postnatal day (P) 8, the WT murine retina was covered with an elongated vessel. L-PGDS deficiency, but not H-PGDS, reduced the physiological vessel elongation with sprouts increase. L-PGDS expression was observed in endothelial cells and neural cells. In vitro, L-PGDS inhibition increased the hypoxia-induced vascular endothelial growth factor expression in isolated endothelial cells, inhibited by a prostaglandin D(2) metabolite, 15-deoxy-Delta(12,14) -PGJ(2) (15d-PGJ(2)) treatment. Pericyte depletion, using antiplatelet-derived growth factor receptor-beta antibody, caused retinal hemorrhage with vessel elongation impairment and macrophage infiltration in the WT P8 retina. H-PGDS deficiency promoted hemorrhage but inhibited the impairment of vessel elongation, while L-PGDS did not. In the pericyte-depleted WT retina, H-PGDS was expressed in the infiltrated macrophages. Deficiency of the D prostanoid receptor also inhibited the vessel elongation impairment. These results suggest the endogenous role of L-PGDS signaling in physiological angiogenesis and that of H-PGDS/D prostanoid 1 signaling in pathological angiogenesis. |
