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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MDPI AG
2022-12-01
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| Series: | Current Issues in Molecular Biology |
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| Online Access: | https://www.mdpi.com/1467-3045/44/12/422 |
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| author | Zhi-Hui Yi Shu-Qing Li Jun-Ya Ke Yun Wang Ming-Zhi Zhao Jing Li Ming-Qing Li Zhi-Ling Zhu |
| author_facet | Zhi-Hui Yi Shu-Qing Li Jun-Ya Ke Yun Wang Ming-Zhi Zhao Jing Li Ming-Qing Li Zhi-Ling Zhu |
| author_sort | Zhi-Hui Yi |
| collection | DOAJ |
| 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 <i>HMOX1</i>, <i>FTH1</i>, and <i>FTL</i> 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 | doaj.art-f859d65b075243f8b53c796daf905b962023-11-24T14:03:47ZengMDPI AGCurrent Issues in Molecular Biology1467-30371467-30452022-12-0144126189620410.3390/cimb44120422Baicalein Relieves Ferroptosis-Mediated Phagocytosis Inhibition of Macrophages in Ovarian EndometriosisZhi-Hui Yi0Shu-Qing Li1Jun-Ya Ke2Yun Wang3Ming-Zhi Zhao4Jing Li5Ming-Qing Li6Zhi-Ling Zhu7Department of Obstetrics and Gynecology, Shanghai Medical College of Fudan University, Shanghai 200011, ChinaDepartment of Obstetrics and Gynecology, Shanghai Medical College of Fudan University, Shanghai 200011, ChinaInstitute of Obstetrics and Gynecology, Hospital of Obstetrics and Gynecology, Fudan University, Shanghai 200080, ChinaDepartment of Obstetrics and Gynecology, Shanghai Medical College of Fudan University, Shanghai 200011, ChinaDepartment of Obstetrics and Gynecology, Shanghai Medical College of Fudan University, Shanghai 200011, ChinaDepartment of Obstetrics and Gynecology, Shanghai Medical College of Fudan University, Shanghai 200011, ChinaDepartment of Obstetrics and Gynecology, Shanghai Medical College of Fudan University, Shanghai 200011, ChinaDepartment of Obstetrics and Gynecology, Shanghai Medical College of Fudan University, Shanghai 200011, ChinaIron 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 <i>HMOX1</i>, <i>FTH1</i>, and <i>FTL</i> 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.https://www.mdpi.com/1467-3045/44/12/422macrophagephagocytosisferroptosisbaicaleinendometriosis |
| spellingShingle | Zhi-Hui Yi Shu-Qing Li Jun-Ya Ke Yun Wang Ming-Zhi Zhao Jing Li Ming-Qing Li Zhi-Ling Zhu Baicalein Relieves Ferroptosis-Mediated Phagocytosis Inhibition of Macrophages in Ovarian Endometriosis Current Issues in Molecular Biology macrophage phagocytosis ferroptosis baicalein 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 | macrophage phagocytosis ferroptosis baicalein endometriosis |
| url | https://www.mdpi.com/1467-3045/44/12/422 |
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