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Excess Heme Promotes the Migration and Infiltration of Macrophages in Endometrial Hyperplasia Complicated with Abnormal Uterine Bleeding

In patients, endometrial hyperplasia (EH) is often accompanied by abnormal uterine bleeding (AUB), which is prone to release large amounts of heme. However, the role of excess heme in the migration and infiltration of immune cells in EH complicated by AUB remains unknown. In this study, 45 patients...

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Autores principales: Ruan, Lu-Yu, Lai, Zhen-Zhen, Shi, Jia-Wei, Yang, Hui-Li, Ye, Jiang-Feng, Xie, Feng, Qiu, Xue-Min, Zhu, Xiao-Yong, Li, Ming-Qing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9221196/
https://www.ncbi.nlm.nih.gov/pubmed/35740976
http://dx.doi.org/10.3390/biom12060849
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author Ruan, Lu-Yu
Lai, Zhen-Zhen
Shi, Jia-Wei
Yang, Hui-Li
Ye, Jiang-Feng
Xie, Feng
Qiu, Xue-Min
Zhu, Xiao-Yong
Li, Ming-Qing
author_facet Ruan, Lu-Yu
Lai, Zhen-Zhen
Shi, Jia-Wei
Yang, Hui-Li
Ye, Jiang-Feng
Xie, Feng
Qiu, Xue-Min
Zhu, Xiao-Yong
Li, Ming-Qing
author_sort Ruan, Lu-Yu
collection PubMed
description In patients, endometrial hyperplasia (EH) is often accompanied by abnormal uterine bleeding (AUB), which is prone to release large amounts of heme. However, the role of excess heme in the migration and infiltration of immune cells in EH complicated by AUB remains unknown. In this study, 45 patients with AUB were divided into three groups: a proliferative phase group (n = 15), a secretory phase group (n = 15) and EH (n = 15). We observed that immune cell subpopulations were significantly different among the three groups, as demonstrated by flow cytometry analysis. Of note, there was a higher infiltration of total immune cells and macrophages in the endometrium of patients with EH. Heme up-regulated the expression of heme oxygenase-1 (HO-1) and nuclear factor erythroid-2-related factor 2 (Nrf2) in endometrial epithelial cells (EECs) in vitro, as well as chemokine (e.g., CCL2, CCL3, CCL5, CXCL8) levels. Additionally, stimulation with heme led to the increased recruitment of THP-1 cells in an indirect EEC-THP-1 co-culture unit. These data suggest that sustained and excessive heme in patients with AUB may recruit macrophages by increasing the levels of several chemokines, contributing to the accumulation and infiltration of macrophages in the endometrium of EH patients, and the key molecules of heme metabolism, HO-1 and Nrf2, are also involved in this regulatory process.
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spelling pubmed-92211962022-06-24 Excess Heme Promotes the Migration and Infiltration of Macrophages in Endometrial Hyperplasia Complicated with Abnormal Uterine Bleeding Ruan, Lu-Yu Lai, Zhen-Zhen Shi, Jia-Wei Yang, Hui-Li Ye, Jiang-Feng Xie, Feng Qiu, Xue-Min Zhu, Xiao-Yong Li, Ming-Qing Biomolecules Article In patients, endometrial hyperplasia (EH) is often accompanied by abnormal uterine bleeding (AUB), which is prone to release large amounts of heme. However, the role of excess heme in the migration and infiltration of immune cells in EH complicated by AUB remains unknown. In this study, 45 patients with AUB were divided into three groups: a proliferative phase group (n = 15), a secretory phase group (n = 15) and EH (n = 15). We observed that immune cell subpopulations were significantly different among the three groups, as demonstrated by flow cytometry analysis. Of note, there was a higher infiltration of total immune cells and macrophages in the endometrium of patients with EH. Heme up-regulated the expression of heme oxygenase-1 (HO-1) and nuclear factor erythroid-2-related factor 2 (Nrf2) in endometrial epithelial cells (EECs) in vitro, as well as chemokine (e.g., CCL2, CCL3, CCL5, CXCL8) levels. Additionally, stimulation with heme led to the increased recruitment of THP-1 cells in an indirect EEC-THP-1 co-culture unit. These data suggest that sustained and excessive heme in patients with AUB may recruit macrophages by increasing the levels of several chemokines, contributing to the accumulation and infiltration of macrophages in the endometrium of EH patients, and the key molecules of heme metabolism, HO-1 and Nrf2, are also involved in this regulatory process. MDPI 2022-06-19 /pmc/articles/PMC9221196/ /pubmed/35740976 http://dx.doi.org/10.3390/biom12060849 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ruan, Lu-Yu
Lai, Zhen-Zhen
Shi, Jia-Wei
Yang, Hui-Li
Ye, Jiang-Feng
Xie, Feng
Qiu, Xue-Min
Zhu, Xiao-Yong
Li, Ming-Qing
Excess Heme Promotes the Migration and Infiltration of Macrophages in Endometrial Hyperplasia Complicated with Abnormal Uterine Bleeding
title Excess Heme Promotes the Migration and Infiltration of Macrophages in Endometrial Hyperplasia Complicated with Abnormal Uterine Bleeding
title_full Excess Heme Promotes the Migration and Infiltration of Macrophages in Endometrial Hyperplasia Complicated with Abnormal Uterine Bleeding
title_fullStr Excess Heme Promotes the Migration and Infiltration of Macrophages in Endometrial Hyperplasia Complicated with Abnormal Uterine Bleeding
title_full_unstemmed Excess Heme Promotes the Migration and Infiltration of Macrophages in Endometrial Hyperplasia Complicated with Abnormal Uterine Bleeding
title_short Excess Heme Promotes the Migration and Infiltration of Macrophages in Endometrial Hyperplasia Complicated with Abnormal Uterine Bleeding
title_sort excess heme promotes the migration and infiltration of macrophages in endometrial hyperplasia complicated with abnormal uterine bleeding
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9221196/
https://www.ncbi.nlm.nih.gov/pubmed/35740976
http://dx.doi.org/10.3390/biom12060849
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