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Effect of high glucose supplementation on pulmonary fibrosis involving reactive oxygen species and TGF-β

This study explored the profibrotic impact of high glucose in the lung and potential mechanisms using latent TGF-β1-induced human epithelial cell pulmonary fibrosis and bleomycin (BLM)-induced pulmonary fibrosis models. Results demonstrated that high glucose administration induced epithelial–mesench...

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Autores principales: Ning, Wenjuan, Xu, Xiaoxiao, Zhou, Shican, Wu, Xiao, Wu, Hang, Zhang, Yijie, Han, Jichang, Wang, Junpeng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9593073/
https://www.ncbi.nlm.nih.gov/pubmed/36304232
http://dx.doi.org/10.3389/fnut.2022.998662
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author Ning, Wenjuan
Xu, Xiaoxiao
Zhou, Shican
Wu, Xiao
Wu, Hang
Zhang, Yijie
Han, Jichang
Wang, Junpeng
author_facet Ning, Wenjuan
Xu, Xiaoxiao
Zhou, Shican
Wu, Xiao
Wu, Hang
Zhang, Yijie
Han, Jichang
Wang, Junpeng
author_sort Ning, Wenjuan
collection PubMed
description This study explored the profibrotic impact of high glucose in the lung and potential mechanisms using latent TGF-β1-induced human epithelial cell pulmonary fibrosis and bleomycin (BLM)-induced pulmonary fibrosis models. Results demonstrated that high glucose administration induced epithelial–mesenchymal transition (EMT) in human epithelial cells in a dose-dependent manner via activating latent TGF-β1, followed by increased expression of mesenchymal-related proteins and decreased expression of epithelial marker protein E-cadherin. Further mechanism analysis showed that administration of high glucose dose-dependently promoted total and mitochondrial reactive oxygen species (ROS) accumulation in human epithelial cells, which promoted latent TGF-β1 activation. However, N-acetyl-L-cysteine, a ROS eliminator, inhibited such effects. An in vivo feed study found that mice given a high-glucose diet had more seriously pathological characteristics of pulmonary fibrosis in BLM-treated mice, including increasing infiltrated inflammatory cells, collagen I deposition, and the expression of mesenchymal-related proteins while decreasing the expression of the epithelial marker E-cadherin. In addition, high glucose intake further increased TGF-β1 concentration and upregulated p-Smad2/3 and snail in lung tissues from BLM-treated mice when compared to BLM-treated mice. Finally, supplementation with high glucose further increased the production of lipid peroxidation metabolite malondialdehyde and decreased superoxide dismutase activity in BLM-treated mice. Collectively, these findings illustrate that high glucose supplementation activates a form of latent TGF-β1 by promoting ROS accumulation and ultimately exacerbates the development of pulmonary fibrosis.
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spelling pubmed-95930732022-10-26 Effect of high glucose supplementation on pulmonary fibrosis involving reactive oxygen species and TGF-β Ning, Wenjuan Xu, Xiaoxiao Zhou, Shican Wu, Xiao Wu, Hang Zhang, Yijie Han, Jichang Wang, Junpeng Front Nutr Nutrition This study explored the profibrotic impact of high glucose in the lung and potential mechanisms using latent TGF-β1-induced human epithelial cell pulmonary fibrosis and bleomycin (BLM)-induced pulmonary fibrosis models. Results demonstrated that high glucose administration induced epithelial–mesenchymal transition (EMT) in human epithelial cells in a dose-dependent manner via activating latent TGF-β1, followed by increased expression of mesenchymal-related proteins and decreased expression of epithelial marker protein E-cadherin. Further mechanism analysis showed that administration of high glucose dose-dependently promoted total and mitochondrial reactive oxygen species (ROS) accumulation in human epithelial cells, which promoted latent TGF-β1 activation. However, N-acetyl-L-cysteine, a ROS eliminator, inhibited such effects. An in vivo feed study found that mice given a high-glucose diet had more seriously pathological characteristics of pulmonary fibrosis in BLM-treated mice, including increasing infiltrated inflammatory cells, collagen I deposition, and the expression of mesenchymal-related proteins while decreasing the expression of the epithelial marker E-cadherin. In addition, high glucose intake further increased TGF-β1 concentration and upregulated p-Smad2/3 and snail in lung tissues from BLM-treated mice when compared to BLM-treated mice. Finally, supplementation with high glucose further increased the production of lipid peroxidation metabolite malondialdehyde and decreased superoxide dismutase activity in BLM-treated mice. Collectively, these findings illustrate that high glucose supplementation activates a form of latent TGF-β1 by promoting ROS accumulation and ultimately exacerbates the development of pulmonary fibrosis. Frontiers Media S.A. 2022-10-11 /pmc/articles/PMC9593073/ /pubmed/36304232 http://dx.doi.org/10.3389/fnut.2022.998662 Text en Copyright © 2022 Ning, Xu, Zhou, Wu, Wu, Zhang, Han and Wang. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Nutrition
Ning, Wenjuan
Xu, Xiaoxiao
Zhou, Shican
Wu, Xiao
Wu, Hang
Zhang, Yijie
Han, Jichang
Wang, Junpeng
Effect of high glucose supplementation on pulmonary fibrosis involving reactive oxygen species and TGF-β
title Effect of high glucose supplementation on pulmonary fibrosis involving reactive oxygen species and TGF-β
title_full Effect of high glucose supplementation on pulmonary fibrosis involving reactive oxygen species and TGF-β
title_fullStr Effect of high glucose supplementation on pulmonary fibrosis involving reactive oxygen species and TGF-β
title_full_unstemmed Effect of high glucose supplementation on pulmonary fibrosis involving reactive oxygen species and TGF-β
title_short Effect of high glucose supplementation on pulmonary fibrosis involving reactive oxygen species and TGF-β
title_sort effect of high glucose supplementation on pulmonary fibrosis involving reactive oxygen species and tgf-β
topic Nutrition
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9593073/
https://www.ncbi.nlm.nih.gov/pubmed/36304232
http://dx.doi.org/10.3389/fnut.2022.998662
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