Inhibition of epithelial–mesenchymal transition in retinal pigment epithelial cells by a retinoic acid receptor-α agonist
Abstract 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) signali...
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Nature Portfolio
2021
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oai:doaj.org-article:16726fbcb8c0478f8a735946649e789b2021-12-02T15:56:49ZInhibition of epithelial–mesenchymal transition in retinal pigment epithelial cells by a retinoic acid receptor-α agonist10.1038/s41598-021-90618-42045-2322https://doaj.org/article/16726fbcb8c0478f8a735946649e789b2021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-90618-4https://doaj.org/toc/2045-2322Abstract 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.Yuka KobayashiKazuhiro TokudaChiemi YamashiroFumiaki HigashijimaTakuya YoshimotoManami OtaTadahiko OgataAtsushige AshimoriMakoto HatanoMasaaki KobayashiSho-Hei UchiMakiko WakutaKazuhiro KimuraNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021) |
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Medicine R Science Q Yuka Kobayashi Kazuhiro Tokuda Chiemi Yamashiro Fumiaki Higashijima Takuya Yoshimoto Manami Ota Tadahiko Ogata Atsushige Ashimori Makoto Hatano Masaaki Kobayashi Sho-Hei Uchi Makiko Wakuta Kazuhiro Kimura Inhibition of epithelial–mesenchymal transition in retinal pigment epithelial cells by a retinoic acid receptor-α agonist |
| description |
Abstract 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. |
| format |
article |
| author |
Yuka Kobayashi Kazuhiro Tokuda Chiemi Yamashiro Fumiaki Higashijima Takuya Yoshimoto Manami Ota Tadahiko Ogata Atsushige Ashimori Makoto Hatano Masaaki Kobayashi Sho-Hei Uchi Makiko Wakuta Kazuhiro Kimura |
| author_facet |
Yuka Kobayashi Kazuhiro Tokuda Chiemi Yamashiro Fumiaki Higashijima Takuya Yoshimoto Manami Ota Tadahiko Ogata Atsushige Ashimori Makoto Hatano Masaaki Kobayashi Sho-Hei Uchi Makiko Wakuta Kazuhiro Kimura |
| author_sort |
Yuka Kobayashi |
| title |
Inhibition of epithelial–mesenchymal transition in retinal pigment epithelial cells by a retinoic acid receptor-α agonist |
| title_short |
Inhibition of epithelial–mesenchymal transition in retinal pigment epithelial cells by a retinoic acid receptor-α agonist |
| title_full |
Inhibition of epithelial–mesenchymal transition in retinal pigment epithelial cells by a retinoic acid receptor-α agonist |
| title_fullStr |
Inhibition of epithelial–mesenchymal transition in retinal pigment epithelial cells by a retinoic acid receptor-α agonist |
| title_full_unstemmed |
Inhibition of epithelial–mesenchymal transition in retinal pigment epithelial cells by a retinoic acid receptor-α agonist |
| title_sort |
inhibition of epithelial–mesenchymal transition in retinal pigment epithelial cells by a retinoic acid receptor-α agonist |
| publisher |
Nature Portfolio |
| publishDate |
2021 |
| url |
https://doaj.org/article/16726fbcb8c0478f8a735946649e789b |
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