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4 results on '"Kazuhiro Tokuda"'

1. Benzalkonium chloride-induced myofibroblastic transdifferentiation of Tenon’s capsule fibroblasts is inhibited by coculture with corneal epithelial cells or by interleukin-10

Author

Chiemi Yamashiro, Kazuhiro Tokuda, Yuka Kobayashi, Fumiaki Higashijima, Takuya Yoshimoto, Manami Ota, Tadahiko Ogata, Atsushige Ashimori, Masaaki Kobayashi, Makoto Hatano, Sho-Hei Uchi, Makiko Wakuta, Shinichiro Teranishi, and Kazuhiro Kimura

Subjects
Medicine, Science
Abstract

Abstract Benzalkonium chloride (BAC) is used as a preservative in eyedrops but induces subconjunctival fibrosis that can result in failure of glaucoma surgery. Tenon’s capsule fibroblasts in subconjunctival tissue interact with the corneal epithelium through tear fluid. With the use of a coculture system, we have now investigated the effect of human corneal epithelial (HCE) cells on myofibroblastic transdifferentiation of human Tenon fibroblasts (HTFs) induced by BAC (5 × 10−6%). Immunofluorescence and immunoblot analyses revealed that the BAC-induced expression of α smooth muscle actin (αSMA) in HTFs was suppressed by coculture of these cells with HCE cells (p

Published
2021
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2. Inhibition of epithelial–mesenchymal transition in retinal pigment epithelial cells by a retinoic acid receptor-α agonist

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, and Kazuhiro Kimura

Subjects
Medicine, Science
Abstract

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.

Published
2021
Full Text
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3. Benzalkonium chloride-induced myofibroblastic transdifferentiation of Tenon’s capsule fibroblasts is inhibited by coculture with corneal epithelial cells or by interleukin-10

Author

Tadahiko Ogata, Manami Ota, Kazuhiro Tokuda, Shinichiro Teranishi, Sho-Hei Uchi, Takuya Yoshimoto, Masaaki Kobayashi, Chiemi Yamashiro, Makoto Hatano, Makiko Wakuta, Atsushige Ashimori, Fumiaki Higashijima, Kazuhiro Kimura, and Yuka Kobayashi

Subjects
Tenon Capsule, Science, Immunofluorescence, Article, Cornea, Benzalkonium chloride, Tenon's capsule, Fibrosis, medicine, Humans, Myofibroblasts, Eye diseases, Cells, Cultured, Corneal epithelium, Cell Proliferation, Multidisciplinary, Molecular medicine, medicine.diagnostic_test, Chemistry, Transdifferentiation, Epithelial Cells, Fibroblasts, medicine.disease, Molecular biology, Actins, Coculture Techniques, Interleukin-10, Interleukin 10, medicine.anatomical_structure, Cell Transdifferentiation, Trans-Activators, Medicine, sense organs, Benzalkonium Compounds, Myofibroblast, medicine.drug, Signal Transduction
Abstract

Benzalkonium chloride (BAC) is used as a preservative in eyedrops but induces subconjunctival fibrosis that can result in failure of glaucoma surgery. Tenon’s capsule fibroblasts in subconjunctival tissue interact with the corneal epithelium through tear fluid. With the use of a coculture system, we have now investigated the effect of human corneal epithelial (HCE) cells on myofibroblastic transdifferentiation of human Tenon fibroblasts (HTFs) induced by BAC (5 × 10−6%). Immunofluorescence and immunoblot analyses revealed that the BAC-induced expression of α smooth muscle actin (αSMA) in HTFs was suppressed by coculture of these cells with HCE cells (p p p p

Published
2021

4. Inhibition of epithelial–mesenchymal transition in retinal pigment epithelial cells by a retinoic acid receptor-α agonist

Author

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, and Manami Ota

Subjects
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
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.

Published
2021

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