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Iron-Storage Protein Ferritin Is Upregulated in Endometriosis and Iron Overload Contributes to a Migratory Phenotype

High levels of iron in the peritoneal cavity during menstruation have been implicated in the pathogenesis of endometriosis. However, whether iron directly affects the growth or migration of human endometriotic cells is poorly understood. This study demonstrated the presence of increased levels of th...

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Autores principales: Woo, Jeong-Hwa, Choi, Youn Seok, Choi, Jung-Hye
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7694081/
https://www.ncbi.nlm.nih.gov/pubmed/33121166
http://dx.doi.org/10.3390/biomedicines8110454
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author Woo, Jeong-Hwa
Choi, Youn Seok
Choi, Jung-Hye
author_facet Woo, Jeong-Hwa
Choi, Youn Seok
Choi, Jung-Hye
author_sort Woo, Jeong-Hwa
collection PubMed
description High levels of iron in the peritoneal cavity during menstruation have been implicated in the pathogenesis of endometriosis. However, whether iron directly affects the growth or migration of human endometriotic cells is poorly understood. This study demonstrated the presence of increased levels of the iron storage protein, ferritin, in the endometriotic tissues of patients with endometriosis. Furthermore, iron treatment stimulated the migration and epithelial–mesenchymal transition (EMT), but not growth, of 12Z human endometriotic cells. The expression of matrix metalloproteinase (MMP)-2/-9 was markedly increased through iron treatment in 12Z cells. Interestingly, intracellular reactive oxygen species (ROS) levels were significantly increased by iron in 12Z cells, and N-acetyl-L-cysteine significantly reduced iron-induced migration and MMP-2/-9 expression. Additionally, iron stimulated the activation of the NFκB pathway, and the activation was associated with iron-induced migration and MMP-2/-9 expression in 12Z cells. Moreover, iron markedly increased EMT and MMP-2/-9 expression in endometriotic lesions in an endometriosis mouse model. Taken together, these results suggest that iron may contribute to the migration abilities of human endometriotic cells via MMP expression through the ROS–NFκB pathway.
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spelling pubmed-76940812020-11-28 Iron-Storage Protein Ferritin Is Upregulated in Endometriosis and Iron Overload Contributes to a Migratory Phenotype Woo, Jeong-Hwa Choi, Youn Seok Choi, Jung-Hye Biomedicines Article High levels of iron in the peritoneal cavity during menstruation have been implicated in the pathogenesis of endometriosis. However, whether iron directly affects the growth or migration of human endometriotic cells is poorly understood. This study demonstrated the presence of increased levels of the iron storage protein, ferritin, in the endometriotic tissues of patients with endometriosis. Furthermore, iron treatment stimulated the migration and epithelial–mesenchymal transition (EMT), but not growth, of 12Z human endometriotic cells. The expression of matrix metalloproteinase (MMP)-2/-9 was markedly increased through iron treatment in 12Z cells. Interestingly, intracellular reactive oxygen species (ROS) levels were significantly increased by iron in 12Z cells, and N-acetyl-L-cysteine significantly reduced iron-induced migration and MMP-2/-9 expression. Additionally, iron stimulated the activation of the NFκB pathway, and the activation was associated with iron-induced migration and MMP-2/-9 expression in 12Z cells. Moreover, iron markedly increased EMT and MMP-2/-9 expression in endometriotic lesions in an endometriosis mouse model. Taken together, these results suggest that iron may contribute to the migration abilities of human endometriotic cells via MMP expression through the ROS–NFκB pathway. MDPI 2020-10-27 /pmc/articles/PMC7694081/ /pubmed/33121166 http://dx.doi.org/10.3390/biomedicines8110454 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Woo, Jeong-Hwa
Choi, Youn Seok
Choi, Jung-Hye
Iron-Storage Protein Ferritin Is Upregulated in Endometriosis and Iron Overload Contributes to a Migratory Phenotype
title Iron-Storage Protein Ferritin Is Upregulated in Endometriosis and Iron Overload Contributes to a Migratory Phenotype
title_full Iron-Storage Protein Ferritin Is Upregulated in Endometriosis and Iron Overload Contributes to a Migratory Phenotype
title_fullStr Iron-Storage Protein Ferritin Is Upregulated in Endometriosis and Iron Overload Contributes to a Migratory Phenotype
title_full_unstemmed Iron-Storage Protein Ferritin Is Upregulated in Endometriosis and Iron Overload Contributes to a Migratory Phenotype
title_short Iron-Storage Protein Ferritin Is Upregulated in Endometriosis and Iron Overload Contributes to a Migratory Phenotype
title_sort iron-storage protein ferritin is upregulated in endometriosis and iron overload contributes to a migratory phenotype
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7694081/
https://www.ncbi.nlm.nih.gov/pubmed/33121166
http://dx.doi.org/10.3390/biomedicines8110454
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