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

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 s...

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Autores principales:	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, Kazuhiro Kimura
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/69aff510c86a4c3895e7441006b58b4d
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spelling	oai:doaj.org-article:69aff510c86a4c3895e7441006b58b4d2021-12-02T18:50:49ZBenzalkonium chloride-induced myofibroblastic transdifferentiation of Tenon’s capsule fibroblasts is inhibited by coculture with corneal epithelial cells or by interleukin-1010.1038/s41598-021-94852-82045-2322https://doaj.org/article/69aff510c86a4c3895e7441006b58b4d2021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-94852-8https://doaj.org/toc/2045-2322Abstract 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.Chiemi YamashiroKazuhiro TokudaYuka KobayashiFumiaki HigashijimaTakuya YoshimotoManami OtaTadahiko OgataAtsushige AshimoriMasaaki KobayashiMakoto HatanoSho-Hei UchiMakiko WakutaShinichiro TeranishiKazuhiro KimuraNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q 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 Kazuhiro Kimura Benzalkonium chloride-induced myofibroblastic transdifferentiation of Tenon’s capsule fibroblasts is inhibited by coculture with corneal epithelial cells or by interleukin-10
description	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 < 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	article
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 Kazuhiro Kimura
author_facet	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 Kazuhiro Kimura
author_sort	Chiemi Yamashiro
title	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_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_sort	benzalkonium chloride-induced myofibroblastic transdifferentiation of tenon’s capsule fibroblasts is inhibited by coculture with corneal epithelial cells or by interleukin-10
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/69aff510c86a4c3895e7441006b58b4d
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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

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