Grape seed proanthocyanidins prevent irradiation-induced differentiation of human lung fibroblasts by ameliorating mitochondrial dysfunction

Abstract Radiation-induced lung fibrosis (RILF) is a long-term adverse effect of curative radiotherapy. The accumulation of myofibroblasts in fibroblastic foci is a pivotal feature of RILF. In the study, we found the inhibitory effect of grape seed proanthocyanidins (GSPs) on irradiation-induced dif...

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Autores principales:	XiaoHong Yang, Tao Liu, Bo Chen, Fangqin Wang, Qunfang Yang, XiaoHong Chen
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0b09411a5a9444bf9621fc194dd0d424
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spelling	oai:doaj.org-article:0b09411a5a9444bf9621fc194dd0d4242021-12-02T16:06:50ZGrape seed proanthocyanidins prevent irradiation-induced differentiation of human lung fibroblasts by ameliorating mitochondrial dysfunction10.1038/s41598-017-00108-92045-2322https://doaj.org/article/0b09411a5a9444bf9621fc194dd0d4242017-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-00108-9https://doaj.org/toc/2045-2322Abstract Radiation-induced lung fibrosis (RILF) is a long-term adverse effect of curative radiotherapy. The accumulation of myofibroblasts in fibroblastic foci is a pivotal feature of RILF. In the study, we found the inhibitory effect of grape seed proanthocyanidins (GSPs) on irradiation-induced differentiation of human fetal lung fibroblasts (HFL1). To explore the mechanism by which GSPs inhibit fibroblast differentiation, we measured the reactive oxygen species (ROS) levels, mitochondrial function, mitochondrial dynamics, glycolysis and the signaling molecules involved in fibroblast transdifferentiation. GSPs significantly reduced the production of cellular and mitochondrial ROS after radiation. The increases in mitochondrial respiration, proton leak, mitochondrial ATP production, lactate release and glucose consumption that occurred in response to irradiation were ameliorated by GSPs. Furthermore, GSPs increased the activity of complex I and improved the mitochondrial dynamics, which were disturbed by irradiation. In addition, the elevation of phosphorylation of p38MAPK and Akt, and Nox4 expression induced by irradiation were attenuated by GSPs. Blocking Nox4 attenuated irradiation-mediated fibroblast differentiation. Taken together, these results indicate that GSPs have the ability to inhibit irradiation-induced fibroblast-to-myofibroblast differentiation by ameliorating mitochondrial dynamics and mitochondrial complex I activity, regulating mitochondrial ROS production, ATP production, lactate release, glucose consumption and thereby inhibiting p38MAPK-Akt-Nox4 pathway.XiaoHong YangTao LiuBo ChenFangqin WangQunfang YangXiaoHong ChenNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q XiaoHong Yang Tao Liu Bo Chen Fangqin Wang Qunfang Yang XiaoHong Chen Grape seed proanthocyanidins prevent irradiation-induced differentiation of human lung fibroblasts by ameliorating mitochondrial dysfunction
description	Abstract Radiation-induced lung fibrosis (RILF) is a long-term adverse effect of curative radiotherapy. The accumulation of myofibroblasts in fibroblastic foci is a pivotal feature of RILF. In the study, we found the inhibitory effect of grape seed proanthocyanidins (GSPs) on irradiation-induced differentiation of human fetal lung fibroblasts (HFL1). To explore the mechanism by which GSPs inhibit fibroblast differentiation, we measured the reactive oxygen species (ROS) levels, mitochondrial function, mitochondrial dynamics, glycolysis and the signaling molecules involved in fibroblast transdifferentiation. GSPs significantly reduced the production of cellular and mitochondrial ROS after radiation. The increases in mitochondrial respiration, proton leak, mitochondrial ATP production, lactate release and glucose consumption that occurred in response to irradiation were ameliorated by GSPs. Furthermore, GSPs increased the activity of complex I and improved the mitochondrial dynamics, which were disturbed by irradiation. In addition, the elevation of phosphorylation of p38MAPK and Akt, and Nox4 expression induced by irradiation were attenuated by GSPs. Blocking Nox4 attenuated irradiation-mediated fibroblast differentiation. Taken together, these results indicate that GSPs have the ability to inhibit irradiation-induced fibroblast-to-myofibroblast differentiation by ameliorating mitochondrial dynamics and mitochondrial complex I activity, regulating mitochondrial ROS production, ATP production, lactate release, glucose consumption and thereby inhibiting p38MAPK-Akt-Nox4 pathway.
format	article
author	XiaoHong Yang Tao Liu Bo Chen Fangqin Wang Qunfang Yang XiaoHong Chen
author_facet	XiaoHong Yang Tao Liu Bo Chen Fangqin Wang Qunfang Yang XiaoHong Chen
author_sort	XiaoHong Yang
title	Grape seed proanthocyanidins prevent irradiation-induced differentiation of human lung fibroblasts by ameliorating mitochondrial dysfunction
title_short	Grape seed proanthocyanidins prevent irradiation-induced differentiation of human lung fibroblasts by ameliorating mitochondrial dysfunction
title_full	Grape seed proanthocyanidins prevent irradiation-induced differentiation of human lung fibroblasts by ameliorating mitochondrial dysfunction
title_fullStr	Grape seed proanthocyanidins prevent irradiation-induced differentiation of human lung fibroblasts by ameliorating mitochondrial dysfunction
title_full_unstemmed	Grape seed proanthocyanidins prevent irradiation-induced differentiation of human lung fibroblasts by ameliorating mitochondrial dysfunction
title_sort	grape seed proanthocyanidins prevent irradiation-induced differentiation of human lung fibroblasts by ameliorating mitochondrial dysfunction
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/0b09411a5a9444bf9621fc194dd0d424
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Grape seed proanthocyanidins prevent irradiation-induced differentiation of human lung fibroblasts by ameliorating mitochondrial dysfunction

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