Attenuation of EMT in RPE cells and subretinal fibrosis by an RAR-γ agonist
作者： Kazuhiro Kimura , Tomoko Orita , Yang Liu , Yang Yang , Kazuhiro Tokuda
DOI: 10.1007/S00109-015-1289-8
关键词: Fibrosis 、 Pathology 、 Retinoic acid receptor 、 p38 mitogen-activated protein kinases 、 Agonist 、 Fibronectin 、 Epithelial–mesenchymal transition 、 Glial fibrillary acidic protein 、 Protein kinase B 、 Cell biology 、 Biology
摘要: Subretinal fibrosis contributes to the loss of vision associated with age-related macular degeneration (AMD). Retinal pigment epithelial (RPE) cells play a key role in pathogenesis AMD including fibrotic reaction. We examined retinoic acid receptor-γ (RAR-γ) epithelial-mesenchymal transition (EMT) and other fibrosis-related processes mouse RPE cultured type I collagen gel. Transforming growth factor-β2 (TGF-β2)–induced gel contraction mediated by was inhibited RAR-γ agonist R667 concentration- time-dependent manner. Expression mesenchymal markers α-smooth muscle actin fibronectin, release interleukin-6, phosphorylation paxillin, mitogen-activated protein kinases (ERK, p38, JNK), Smad2, AKT induced TGF-β2 were also suppressed agonist. Furthermore, gelatin zymography immunoblot analysis revealed that TGF-β2-induced matrix metalloproteinase (MMP)-2, MMP-3, MMP-8, MMP-9 from R667, MMP inhibitor GM6001 attenuated cell contraction. Finally, immunohistofluorescence antibodies glial fibrillary acidic showed development subretinal model vivo. Our results thus suggest agonists may prove effective for treatment AMD.
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