| 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
|
| リソース情報 |
| 実験動物マウス |
RBRC00067 |
