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Quercetin Attenuates Lactate Production and Extracellular Matrix Secretion in Keratoconus
Keratoconus(KC) is an ecstatic corneal disease leading to corneal-thinning and the formation of a cone-like cornea. Elevated lactate levels, increased oxidative stress, and myofibroblast formation have all been previously reported. In the current study, we assess the role of Quercetin on collagen se...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4355637/ https://www.ncbi.nlm.nih.gov/pubmed/25758533 http://dx.doi.org/10.1038/srep09003 |
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author | McKay, T. B. Lyon, D. Sarker-Nag, A. Priyadarsini, S. Asara, J. M. Karamichos, D. |
author_facet | McKay, T. B. Lyon, D. Sarker-Nag, A. Priyadarsini, S. Asara, J. M. Karamichos, D. |
author_sort | McKay, T. B. |
collection | PubMed |
description | Keratoconus(KC) is an ecstatic corneal disease leading to corneal-thinning and the formation of a cone-like cornea. Elevated lactate levels, increased oxidative stress, and myofibroblast formation have all been previously reported. In the current study, we assess the role of Quercetin on collagen secretion and myofibroblast formation in KC in vitro. Human corneal fibroblasts(HCFs) and human keratoconus cells(HKCs) were treated with a stable Vitamin C derivative and cultured for 4 weeks, stimulating formation of a self-assembled extracellular matrix. All samples were analyzed using Western blots and targeted tandem mass spectrometry. Our data showed that Quercetin significantly down regulates myofibroblast differentiation and fibrotic markers, such as α-smooth muscle actin (α-SMA) and Collagen III (Col III), in both HCFs and HKCs. Collagen III secretion was reduced 80% in both HCFs and HKCs following Quercetin treatment. Furthermore, Quercetin reduced lactate production by HKCs to normal HCF levels. Quercetin down regulated TGF-βR2 and TGF-β2 expression in HKCs suggesting a significant link to the TGF-β pathway. These results assert that Quercetin is a key regulator of fibrotic markers and ECM assembly by modulating cellular metabolism and TGF-β signaling. Our study suggests that Quercetin is a potential therapeutic for treatment of corneal dystrophies, such as KC. |
format | Online Article Text |
id | pubmed-4355637 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-43556372015-03-17 Quercetin Attenuates Lactate Production and Extracellular Matrix Secretion in Keratoconus McKay, T. B. Lyon, D. Sarker-Nag, A. Priyadarsini, S. Asara, J. M. Karamichos, D. Sci Rep Article Keratoconus(KC) is an ecstatic corneal disease leading to corneal-thinning and the formation of a cone-like cornea. Elevated lactate levels, increased oxidative stress, and myofibroblast formation have all been previously reported. In the current study, we assess the role of Quercetin on collagen secretion and myofibroblast formation in KC in vitro. Human corneal fibroblasts(HCFs) and human keratoconus cells(HKCs) were treated with a stable Vitamin C derivative and cultured for 4 weeks, stimulating formation of a self-assembled extracellular matrix. All samples were analyzed using Western blots and targeted tandem mass spectrometry. Our data showed that Quercetin significantly down regulates myofibroblast differentiation and fibrotic markers, such as α-smooth muscle actin (α-SMA) and Collagen III (Col III), in both HCFs and HKCs. Collagen III secretion was reduced 80% in both HCFs and HKCs following Quercetin treatment. Furthermore, Quercetin reduced lactate production by HKCs to normal HCF levels. Quercetin down regulated TGF-βR2 and TGF-β2 expression in HKCs suggesting a significant link to the TGF-β pathway. These results assert that Quercetin is a key regulator of fibrotic markers and ECM assembly by modulating cellular metabolism and TGF-β signaling. Our study suggests that Quercetin is a potential therapeutic for treatment of corneal dystrophies, such as KC. Nature Publishing Group 2015-03-11 /pmc/articles/PMC4355637/ /pubmed/25758533 http://dx.doi.org/10.1038/srep09003 Text en Copyright © 2015, Macmillan Publishers Limited. All rights reserved http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder in order to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article McKay, T. B. Lyon, D. Sarker-Nag, A. Priyadarsini, S. Asara, J. M. Karamichos, D. Quercetin Attenuates Lactate Production and Extracellular Matrix Secretion in Keratoconus |
title | Quercetin Attenuates Lactate Production and Extracellular Matrix Secretion in Keratoconus |
title_full | Quercetin Attenuates Lactate Production and Extracellular Matrix Secretion in Keratoconus |
title_fullStr | Quercetin Attenuates Lactate Production and Extracellular Matrix Secretion in Keratoconus |
title_full_unstemmed | Quercetin Attenuates Lactate Production and Extracellular Matrix Secretion in Keratoconus |
title_short | Quercetin Attenuates Lactate Production and Extracellular Matrix Secretion in Keratoconus |
title_sort | quercetin attenuates lactate production and extracellular matrix secretion in keratoconus |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4355637/ https://www.ncbi.nlm.nih.gov/pubmed/25758533 http://dx.doi.org/10.1038/srep09003 |
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