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Baicalein Relieves Ferroptosis-Mediated Phagocytosis Inhibition of Macrophages in Ovarian Endometriosis

Iron overload and oxidative stress have been reported to contribute to ferroptosis in endometriotic lesions. However, the possible roles of iron overload on macrophages in endometriosis (EMs) remain unknown. Based on recent reports by single-cell sequencing data of endometriosis, here we found signi...

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Autores principales: Yi, Zhi-Hui, Li, Shu-Qing, Ke, Jun-Ya, Wang, Yun, Zhao, Ming-Zhi, Li, Jing, Li, Ming-Qing, Zhu, Zhi-Ling
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9777460/
https://www.ncbi.nlm.nih.gov/pubmed/36547083
http://dx.doi.org/10.3390/cimb44120422
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author Yi, Zhi-Hui
Li, Shu-Qing
Ke, Jun-Ya
Wang, Yun
Zhao, Ming-Zhi
Li, Jing
Li, Ming-Qing
Zhu, Zhi-Ling
author_facet Yi, Zhi-Hui
Li, Shu-Qing
Ke, Jun-Ya
Wang, Yun
Zhao, Ming-Zhi
Li, Jing
Li, Ming-Qing
Zhu, Zhi-Ling
author_sort Yi, Zhi-Hui
collection PubMed
description Iron overload and oxidative stress have been reported to contribute to ferroptosis in endometriotic lesions. However, the possible roles of iron overload on macrophages in endometriosis (EMs) remain unknown. Based on recent reports by single-cell sequencing data of endometriosis, here we found significant upregulations of ferroptosis-associated genes in the macrophage of the endometriotic lesion. Additionally, there was an elevated expression of HMOX1, FTH1, and FTL in macrophages of peritoneal fluid in EMs, as well as iron accumulation in the endometriotic lesions. Notably, cyst fluid significantly up-regulated levels of intracellular iron and ferroptosis in Phorbol-12-myristate-13-acetate (PMA)-stimulated THP-1 cells. Additionally, high iron-induced ferroptosis obviously reduced PMA-stimulated THP-1 cells’ phagocytosis and increased the expression of angiogenic cytokines, such as vascular endothelial growth factor A (VEGFA) and interleukin 8 (IL8). Baicalein, a potential anti-ferroptosis compound, increased GPX4 expression, significantly inhibited ferroptosis, and restored phagocytosis of THP-1 cells in vitro. Collectively, our study reveals that ferroptosis triggered by high iron in cyst fluid promotes the development of EMs by impairing macrophage phagocytosis and producing more angiogenic cytokines (e.g., IL8 and VEGFA). Baicalein displays the potential for the treatment of EMs, especially in patients with high ferroptosis and low phagocytosis of macrophages.
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spelling pubmed-97774602022-12-23 Baicalein Relieves Ferroptosis-Mediated Phagocytosis Inhibition of Macrophages in Ovarian Endometriosis Yi, Zhi-Hui Li, Shu-Qing Ke, Jun-Ya Wang, Yun Zhao, Ming-Zhi Li, Jing Li, Ming-Qing Zhu, Zhi-Ling Curr Issues Mol Biol Article Iron overload and oxidative stress have been reported to contribute to ferroptosis in endometriotic lesions. However, the possible roles of iron overload on macrophages in endometriosis (EMs) remain unknown. Based on recent reports by single-cell sequencing data of endometriosis, here we found significant upregulations of ferroptosis-associated genes in the macrophage of the endometriotic lesion. Additionally, there was an elevated expression of HMOX1, FTH1, and FTL in macrophages of peritoneal fluid in EMs, as well as iron accumulation in the endometriotic lesions. Notably, cyst fluid significantly up-regulated levels of intracellular iron and ferroptosis in Phorbol-12-myristate-13-acetate (PMA)-stimulated THP-1 cells. Additionally, high iron-induced ferroptosis obviously reduced PMA-stimulated THP-1 cells’ phagocytosis and increased the expression of angiogenic cytokines, such as vascular endothelial growth factor A (VEGFA) and interleukin 8 (IL8). Baicalein, a potential anti-ferroptosis compound, increased GPX4 expression, significantly inhibited ferroptosis, and restored phagocytosis of THP-1 cells in vitro. Collectively, our study reveals that ferroptosis triggered by high iron in cyst fluid promotes the development of EMs by impairing macrophage phagocytosis and producing more angiogenic cytokines (e.g., IL8 and VEGFA). Baicalein displays the potential for the treatment of EMs, especially in patients with high ferroptosis and low phagocytosis of macrophages. MDPI 2022-12-07 /pmc/articles/PMC9777460/ /pubmed/36547083 http://dx.doi.org/10.3390/cimb44120422 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
Yi, Zhi-Hui
Li, Shu-Qing
Ke, Jun-Ya
Wang, Yun
Zhao, Ming-Zhi
Li, Jing
Li, Ming-Qing
Zhu, Zhi-Ling
Baicalein Relieves Ferroptosis-Mediated Phagocytosis Inhibition of Macrophages in Ovarian Endometriosis
title Baicalein Relieves Ferroptosis-Mediated Phagocytosis Inhibition of Macrophages in Ovarian Endometriosis
title_full Baicalein Relieves Ferroptosis-Mediated Phagocytosis Inhibition of Macrophages in Ovarian Endometriosis
title_fullStr Baicalein Relieves Ferroptosis-Mediated Phagocytosis Inhibition of Macrophages in Ovarian Endometriosis
title_full_unstemmed Baicalein Relieves Ferroptosis-Mediated Phagocytosis Inhibition of Macrophages in Ovarian Endometriosis
title_short Baicalein Relieves Ferroptosis-Mediated Phagocytosis Inhibition of Macrophages in Ovarian Endometriosis
title_sort baicalein relieves ferroptosis-mediated phagocytosis inhibition of macrophages in ovarian endometriosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9777460/
https://www.ncbi.nlm.nih.gov/pubmed/36547083
http://dx.doi.org/10.3390/cimb44120422
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