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Benzalkonium chloride-induced myofibroblastic transdifferentiation of Tenon’s capsule fibroblasts is inhibited by coculture with corneal epithelial cells or by interleukin-10
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...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8352883/ https://www.ncbi.nlm.nih.gov/pubmed/34373467 http://dx.doi.org/10.1038/s41598-021-94852-8 |
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author | Yamashiro, Chiemi Tokuda, Kazuhiro Kobayashi, Yuka Higashijima, Fumiaki Yoshimoto, Takuya Ota, Manami Ogata, Tadahiko Ashimori, Atsushige Kobayashi, Masaaki Hatano, Makoto Uchi, Sho-Hei Wakuta, Makiko Teranishi, Shinichiro Kimura, Kazuhiro |
author_facet | Yamashiro, Chiemi Tokuda, Kazuhiro Kobayashi, Yuka Higashijima, Fumiaki Yoshimoto, Takuya Ota, Manami Ogata, Tadahiko Ashimori, Atsushige Kobayashi, Masaaki Hatano, Makoto Uchi, Sho-Hei Wakuta, Makiko Teranishi, Shinichiro Kimura, Kazuhiro |
author_sort | Yamashiro, Chiemi |
collection | PubMed |
description | 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 < 0.01). The concentration of interleukin-10 (IL-10) in culture supernatants of BAC-treated HTFs was increased by coculture with HCE cells (17.26-fold, vs. coculure, p < 0.001). Immunofluorescence and immunoblot analyses also showed that exogenous IL-10 (300 pg/ml) suppressed the BAC-induced expression of αSMA by 43.65% (p < 0.05) as well as the nuclear translocation of myocardin-related transcription factor-A (MRTF-A) by 39.32% (p < 0.01) in HTFs cultured alone. Our findings suggest that corneal epithelial cells may protect against subconjunctival fibrosis by maintaining IL-10 levels and preventing the MRTF-A-dependent transdifferentiation of HTFs into myofibroblasts. |
format | Online Article Text |
id | pubmed-8352883 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-83528832021-08-10 Benzalkonium chloride-induced myofibroblastic transdifferentiation of Tenon’s capsule fibroblasts is inhibited by coculture with corneal epithelial cells or by interleukin-10 Yamashiro, Chiemi Tokuda, Kazuhiro Kobayashi, Yuka Higashijima, Fumiaki Yoshimoto, Takuya Ota, Manami Ogata, Tadahiko Ashimori, Atsushige Kobayashi, Masaaki Hatano, Makoto Uchi, Sho-Hei Wakuta, Makiko Teranishi, Shinichiro Kimura, Kazuhiro Sci Rep Article 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 < 0.01). The concentration of interleukin-10 (IL-10) in culture supernatants of BAC-treated HTFs was increased by coculture with HCE cells (17.26-fold, vs. coculure, p < 0.001). Immunofluorescence and immunoblot analyses also showed that exogenous IL-10 (300 pg/ml) suppressed the BAC-induced expression of αSMA by 43.65% (p < 0.05) as well as the nuclear translocation of myocardin-related transcription factor-A (MRTF-A) by 39.32% (p < 0.01) in HTFs cultured alone. Our findings suggest that corneal epithelial cells may protect against subconjunctival fibrosis by maintaining IL-10 levels and preventing the MRTF-A-dependent transdifferentiation of HTFs into myofibroblasts. Nature Publishing Group UK 2021-08-09 /pmc/articles/PMC8352883/ /pubmed/34373467 http://dx.doi.org/10.1038/s41598-021-94852-8 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Yamashiro, Chiemi Tokuda, Kazuhiro Kobayashi, Yuka Higashijima, Fumiaki Yoshimoto, Takuya Ota, Manami Ogata, Tadahiko Ashimori, Atsushige Kobayashi, Masaaki Hatano, Makoto Uchi, Sho-Hei Wakuta, Makiko Teranishi, Shinichiro Kimura, Kazuhiro Benzalkonium chloride-induced myofibroblastic transdifferentiation of Tenon’s capsule fibroblasts is inhibited by coculture with corneal epithelial cells or by interleukin-10 |
title | Benzalkonium chloride-induced myofibroblastic transdifferentiation of Tenon’s capsule fibroblasts is inhibited by coculture with corneal epithelial cells or by interleukin-10 |
title_full | Benzalkonium chloride-induced myofibroblastic transdifferentiation of Tenon’s capsule fibroblasts is inhibited by coculture with corneal epithelial cells or by interleukin-10 |
title_fullStr | Benzalkonium chloride-induced myofibroblastic transdifferentiation of Tenon’s capsule fibroblasts is inhibited by coculture with corneal epithelial cells or by interleukin-10 |
title_full_unstemmed | Benzalkonium chloride-induced myofibroblastic transdifferentiation of Tenon’s capsule fibroblasts is inhibited by coculture with corneal epithelial cells or by interleukin-10 |
title_short | Benzalkonium chloride-induced myofibroblastic transdifferentiation of Tenon’s capsule fibroblasts is inhibited by coculture with corneal epithelial cells or by interleukin-10 |
title_sort | benzalkonium chloride-induced myofibroblastic transdifferentiation of tenon’s capsule fibroblasts is inhibited by coculture with corneal epithelial cells or by interleukin-10 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8352883/ https://www.ncbi.nlm.nih.gov/pubmed/34373467 http://dx.doi.org/10.1038/s41598-021-94852-8 |
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