Inhibition of epithelial–mesenchymal transition in retinal pigment epithelial cells by a retinoic acid receptor-α agonist
| Autor: | Takuya Yoshimoto, Tadahiko Ogata, Atsushige Ashimori, Masaaki Kobayashi, Kazuhiro Kimura, Sho-Hei Uchi, Makoto Hatano, Chiemi Yamashiro, Makiko Wakuta, Kazuhiro Tokuda, Yuka Kobayashi, Fumiaki Higashijima, Manami Ota |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Epithelial-Mesenchymal Transition Tetrahydronaphthalenes Science Retinal Pigment Epithelium Smad2 Protein Benzoates Article Focal adhesion Mice Transforming Growth Factor beta2 03 medical and health sciences chemistry.chemical_compound Medical research 0302 clinical medicine Fibrosis medicine Animals Epithelial–mesenchymal transition Phosphorylation Eye diseases Paxillin Cell Proliferation Multidisciplinary biology Interleukin-6 Retinoic Acid Receptor alpha Muscle Smooth Retinal medicine.disease Actins Cell biology Mice Inbred C57BL Fibronectin Retinoic acid receptor 030104 developmental biology chemistry Trans-Activators 030221 ophthalmology & optometry biology.protein Medicine Female Collagen Type I collagen Signal Transduction |
| Zdroj: | Scientific Reports, Vol 11, Iss 1, Pp 1-13 (2021) Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | Epithelial–mesenchymal transition (EMT) in retinal pigment epithelial (RPE) cells plays a key role in proliferative retinal diseases such as age-related macular degeneration by contributing to subretinal fibrosis. To investigate the potential role of retinoic acid receptor-α (RAR-α) signaling in this process, we have now examined the effects of the RAR-α agonist Am580 on EMT induced by transforming growth factor-β2 (TGF-β2) in primary mouse RPE cells cultured in a three-dimensional type I collagen gel as well as on subretinal fibrosis in a mouse model. We found that Am580 inhibited TGF-β2-induced collagen gel contraction mediated by RPE cells. It also attenuated the TGF-β2-induced expression of the mesenchymal markers α-smooth muscle actin, fibronectin, and collagen type I; production of pro-matrix metalloproteinase 2 and interleukin-6; expression of the focal adhesion protein paxillin; and phosphorylation of SMAD2 in the cultured RPE cells. Finally, immunofluorescence analysis showed that Am580 suppressed both the TGF-β2-induced translocation of myocardin-related transcription factor-A (MRTF-A) from the cytoplasm to the nucleus of cultured RPE cells as well as subretinal fibrosis triggered by laser-induced photocoagulation in a mouse model. Our observations thus suggest that RAR-α signaling inhibits EMT in RPE cells and might attenuate the development of fibrosis associated with proliferative retinal diseases. |
| Databáze: | OpenAIRE |
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