Nitric oxide attenuated transforming growth factor-β induced myofibroblast differentiation of human keratocytes

Abstract Nitric oxide (NO) has the potential to modulate myofibroblast differentiation. In this study, we investigated the effect of exogenous NO on the myofibroblast differentiation of human keratocytes using sodium nitrite as a NO donor. Myofibroblasts were induced by exposing resting keratocytes...

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Autores principales:	Joo-Hee Park, Martha Kim, Bora Yim, Choul Yong Park
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/32c3ee4e12a9437c8e9364aab37a254e
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spelling	oai:doaj.org-article:32c3ee4e12a9437c8e9364aab37a254e2021-12-02T14:27:56ZNitric oxide attenuated transforming growth factor-β induced myofibroblast differentiation of human keratocytes10.1038/s41598-021-87791-x2045-2322https://doaj.org/article/32c3ee4e12a9437c8e9364aab37a254e2021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-87791-xhttps://doaj.org/toc/2045-2322Abstract Nitric oxide (NO) has the potential to modulate myofibroblast differentiation. In this study, we investigated the effect of exogenous NO on the myofibroblast differentiation of human keratocytes using sodium nitrite as a NO donor. Myofibroblasts were induced by exposing resting keratocytes to transforming growth factor (TGF)-β1. N-cadherin and α-smooth muscle actin (αSMA) were used as myofibroblast markers. Both resting keratocytes and -stimulated keratocytes were exposed to various concentrations of sodium nitrite (1 μM to 1000 mM) for 24 to 72 h. Exposure to sodium nitrite did not alter keratocytes’ viability up to a 10 mM concentration for 72 h. However, significant cytotoxicity was observed in higher concentrations of sodium nitrite (over 100 mM). The expression of αSMA and N-cadherin was significantly increased in keratocytes by TGF-β1 stimulation after 72 h incubation. The addition of sodium nitrite (1 mM) to TGF-β1-stimulated keratocytes significantly decreased αSMA and N cadherin expression. Smad3 phosphorylation decreased after sodium nitrite (1 mM) exposure in TGF-β1-stimulated keratocytes. The effect of NO was reversed when NO scavenger, 2-4-carboxyphenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO) was added in the culture medium. Application of sodium nitrite resulted in significant decrease of corneal opacity when measured at 2 weeks after the chemical burn in the mouse. These results verified the potential therapeutic effect of NO to decrease myofibroblast differentiation of human keratocytes and corneal opacity after injury.Joo-Hee ParkMartha KimBora YimChoul Yong ParkNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Joo-Hee Park Martha Kim Bora Yim Choul Yong Park Nitric oxide attenuated transforming growth factor-β induced myofibroblast differentiation of human keratocytes
description	Abstract Nitric oxide (NO) has the potential to modulate myofibroblast differentiation. In this study, we investigated the effect of exogenous NO on the myofibroblast differentiation of human keratocytes using sodium nitrite as a NO donor. Myofibroblasts were induced by exposing resting keratocytes to transforming growth factor (TGF)-β1. N-cadherin and α-smooth muscle actin (αSMA) were used as myofibroblast markers. Both resting keratocytes and -stimulated keratocytes were exposed to various concentrations of sodium nitrite (1 μM to 1000 mM) for 24 to 72 h. Exposure to sodium nitrite did not alter keratocytes’ viability up to a 10 mM concentration for 72 h. However, significant cytotoxicity was observed in higher concentrations of sodium nitrite (over 100 mM). The expression of αSMA and N-cadherin was significantly increased in keratocytes by TGF-β1 stimulation after 72 h incubation. The addition of sodium nitrite (1 mM) to TGF-β1-stimulated keratocytes significantly decreased αSMA and N cadherin expression. Smad3 phosphorylation decreased after sodium nitrite (1 mM) exposure in TGF-β1-stimulated keratocytes. The effect of NO was reversed when NO scavenger, 2-4-carboxyphenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO) was added in the culture medium. Application of sodium nitrite resulted in significant decrease of corneal opacity when measured at 2 weeks after the chemical burn in the mouse. These results verified the potential therapeutic effect of NO to decrease myofibroblast differentiation of human keratocytes and corneal opacity after injury.
format	article
author	Joo-Hee Park Martha Kim Bora Yim Choul Yong Park
author_facet	Joo-Hee Park Martha Kim Bora Yim Choul Yong Park
author_sort	Joo-Hee Park
title	Nitric oxide attenuated transforming growth factor-β induced myofibroblast differentiation of human keratocytes
title_short	Nitric oxide attenuated transforming growth factor-β induced myofibroblast differentiation of human keratocytes
title_full	Nitric oxide attenuated transforming growth factor-β induced myofibroblast differentiation of human keratocytes
title_fullStr	Nitric oxide attenuated transforming growth factor-β induced myofibroblast differentiation of human keratocytes
title_full_unstemmed	Nitric oxide attenuated transforming growth factor-β induced myofibroblast differentiation of human keratocytes
title_sort	nitric oxide attenuated transforming growth factor-β induced myofibroblast differentiation of human keratocytes
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/32c3ee4e12a9437c8e9364aab37a254e
work_keys_str_mv	AT jooheepark nitricoxideattenuatedtransforminggrowthfactorbinducedmyofibroblastdifferentiationofhumankeratocytes AT marthakim nitricoxideattenuatedtransforminggrowthfactorbinducedmyofibroblastdifferentiationofhumankeratocytes AT borayim nitricoxideattenuatedtransforminggrowthfactorbinducedmyofibroblastdifferentiationofhumankeratocytes AT choulyongpark nitricoxideattenuatedtransforminggrowthfactorbinducedmyofibroblastdifferentiationofhumankeratocytes
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Nitric oxide attenuated transforming growth factor-β induced myofibroblast differentiation of human keratocytes

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