論文 - 詳細
| RRC ID | 46789 |
|---|---|
| 著者 | Kobayashi Y, Yoshida S, Zhou Y, Nakama T, Ishikawa K, Kubo Y, Arima M, Nakao S, Hisatomi T, Ikeda Y, Matsuda A, Sonoda KH, Ishibashi T. |
| タイトル | Tenascin-C secreted by transdifferentiated retinal pigment epithelial cells promotes choroidal neovascularization via integrin αV. |
| ジャーナル | Lab Invest |
| Abstract |
Tenascin-C is expressed in choroidal neovascular (CNV) membranes in eyes with age-related macular degeneration (AMD). However, its role in the pathogenesis of CNV remains to be elucidated. Here we investigated the role of tenascin-C in CNV formation. In immunofluorescence analyses, tenascin-C co-stained with α-SMA, pan-cytokeratin, CD31, CD34, and integrin αV in the CNV membranes of patients with AMD and a mouse model of laser-induced CNV. A marked increase in the expression of tenascin-C mRNA and protein was observed 3 days after laser photocoagulation in the mouse CNV model. Tenascin-C was also shown to promote proliferation and inhibit adhesion of human retinal pigment epithelial (hRPE) cells in vitro. Moreover, tenascin-C promoted proliferation, adhesion, migration, and tube formation in human microvascular endothelial cells (HMVECs); these functions were, however, blocked by cilengitide, an integrin αV inhibitor. Exposure to TGF-β2 increased tenascin-C expression in hRPE cells. Conditioned media harvested from TGF-β2-treated hRPE cell cultures enhanced HMVEC proliferation and tube formation, which were inhibited by pretreatment with tenascin-C siRNA. The CNV volume was significantly reduced in tenascin-C knockout mice and tenascin-C siRNA-injected mice. These findings suggest that tenascin-C is secreted by transdifferentiated RPE cells and promotes the development of CNV via integrin αV in a paracrine manner. Therefore, tenascin-C could be a potential therapeutic target for the inhibition of CNV development associated with AMD. |
| 巻・号 | 96(11) |
| ページ | 1178-1188 |
| 公開日 | 2016-11-1 |
| DOI | 10.1038/labinvest.2016.99 |
| PII | labinvest201699 |
| PMID | 27668890 |
| MeSH | Aged Aged, 80 and over Animals Cell Physiological Phenomena Cell Transdifferentiation Choroidal Neovascularization / metabolism* Disease Models, Animal Endothelial Cells / metabolism Humans Integrin alphaV / metabolism Mice Mice, Inbred C57BL Mice, Knockout Middle Aged Myofibroblasts / metabolism Neovascularization, Pathologic Retinal Pigment Epithelium / metabolism* Tenascin / metabolism* Transforming Growth Factor beta2 |
| IF | 4.197 |
| 引用数 | 8 |
| WOS 分野 | MEDICINE, RESEARCH & EXPERIMENTAL 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 | News |
| 各媒体での言及数の合計 | 3 |
| 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 | |
| 実験動物マウス | RBRC00067 |