論文 - 詳細
| RRC ID | 44377 |
|---|---|
| 著者 | Iesato Y, Toriyama Y, Sakurai T, Kamiyoshi A, Ichikawa-Shindo Y, Kawate H, Yoshizawa T, Koyama T, Uetake R, Yang L, Yamauchi A, Tanaka M, Igarashi K, Murata T, Shindo T. |
| タイトル | Adrenomedullin-RAMP2 system is crucially involved in retinal angiogenesis. |
| ジャーナル | Am J Pathol |
| Abstract |
Adrenomedullin (ADM) is an endogenous peptide first identified as a strong vasodilating molecule. We previously showed that in mice, homozygous knockout of ADM (ADM(-/-)) or its receptor regulating protein, RAMP2 (RAMP2(-/-)), is embryonically lethal due to abnormal vascular development, thereby demonstrating the importance of ADM and its receptor signaling to vascular development. ADM expression in the retina is strongly induced by ischemia; however, its role in retinal pathophysiology remains unknown. Here, we analyzed oxygen-induced retinopathy (OIR) using heterozygous ADM and RAMP2 knockout mice models (ADM(+/-) or RAMP2(+/-), respectively). In addition, we analyzed the role of the ADM-RAMP2 system during earlier stages of retinal angiogenesis using an inducible endothelial cell-specific RAMP2 knockout mouse line (DI-E-RAMP2(-/-)). Finally, we assessed the ability of antibody-induced ADM blockade to control pathological retinal angiogenesis in OIR. In OIR, neovascular tufts, avascular zones, and hypoxic areas were all smaller in ADM(+/-) retinas compared with wild-type mice. ADM(+/-) retinas also exhibited reduced levels of VEGF and eNOS expression. DI-E-RAMP2(-/-) showed abnormal retinal vascular patterns in the early stages of development. However, ADM enhanced the proliferation and migration of retinal endothelial cells. Finally, we found intravitreal injection of anti-ADM antibody reduced pathological retinal angiogenesis. In conclusion, the ADM-RAMP2 system is crucially involved in retinal angiogenesis. ADM and its receptor system are potential therapeutic targets for controlling pathological retinal angiogenesis. |
| 巻・号 | 182(6) |
| ページ | 2380-90 |
| 公開日 | 2013-6-1 |
| DOI | 10.1016/j.ajpath.2013.02.015 |
| PII | S0002-9440(13)00193-4 |
| PMID | 23562442 |
| MeSH | Adrenomedullin / antagonists & inhibitors Adrenomedullin / deficiency Adrenomedullin / genetics Adrenomedullin / physiology* Animals Antibodies, Monoclonal / therapeutic use Cell Hypoxia / physiology Cell Movement / physiology Cell Proliferation Cells, Cultured Endothelial Cells / physiology Fetal Development / physiology Gene Expression Regulation / physiology Intravitreal Injections Mice Mice, Inbred C57BL Mice, Knockout RNA, Messenger / genetics Receptor Activity-Modifying Protein 2 / deficiency Receptor Activity-Modifying Protein 2 / genetics Receptor Activity-Modifying Protein 2 / physiology* Retina / embryology Retina / metabolism Retina / pathology Retinal Neovascularization / metabolism Retinal Neovascularization / pathology Retinal Neovascularization / physiopathology* Retinal Neovascularization / prevention & control Retinal Vessels / pathology |
| IF | 3.491 |
| 引用数 | 13 |
| WOS 分野 | PATHOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | RF/6A 135(RCB1556) |