論文 - 詳細
| RRC ID | 72001 |
|---|---|
| 著者 | Koya Y, Nara H, Yagi S, Ueno C, Kamohara M. |
| タイトル | An engineered tetra-valent antibody fully activates the Tie2 receptor with comparable potency to its natural ligand angiopoietin-1. |
| ジャーナル | Sci Rep |
| Abstract |
Activation of the tyrosine kinase with Ig and epidermal growth factor homology domain 2 (Tie2) receptor by angiopoietin-1 (Ang1) is critical for vascular stabilization: it promotes survival signal transduction via auto-phosphorylation and reduces vascular permeability by strengthening tight junctions between endothelial cells. Thus, Tie2/Ang1 signaling is a promising therapeutic target for vascular diseases. However, in vivo use of existing Tie2 signaling modulators, such as recombinant Ang1, is restricted by limitations in manufacturability and stability. Here, we present a novel engineered tetra-valent agonistic antibody, ASP4021, which can specifically and fully activate the Tie2 receptor in an equivalent manner to Ang1. ASP4021 induced Tie2 self-phosphorylation and inhibited apoptosis in a human primary endothelial cell line. Additionally, single administration of ASP4021 significantly suppressed mustard-oil-induced vascular permeability in rats. ASP4021 may thus be a potential therapeutic candidate for diseases associated with vascular weakness such as diabetic retinopathy, diabetic macular edema and critical limb ischemia. |
| 巻・号 | 11(1) |
| ページ | 14021 |
| 公開日 | 2021-7-7 |
| DOI | 10.1038/s41598-021-93660-4 |
| PII | 10.1038/s41598-021-93660-4 |
| PMID | 34234265 |
| PMC | PMC8263585 |
| MeSH | Angiopoietin-1 / metabolism* Angiopoietin-1 / pharmacology Animals Antibodies / genetics Antibodies / pharmacology* Apoptosis / drug effects Capillary Permeability / drug effects Genetic Engineering Humans Ligands Male Mice Phosphorylation Rats Receptor, TIE-2 / agonists* Recombinant Fusion Proteins / genetics Recombinant Fusion Proteins / pharmacology* |
| IF | 3.998 |
| 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 | 7 |
| 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 | Ba/F3(RCB0805) |