High taurocholic acid concentration induces ferroptosis by downregulating FTH1 expression in intrahepatic cholestasis of pregnancy
Abstract Background Intrahepatic cholestasis of pregnancy (ICP) is the most common liver disorder associated with pregnancy and is usually diagnosed based on high serum bile acid. However, the pathogenesis of ICP is unclear. Ferroptosis has been reported as an iron-dependent mechanism of cell death....
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BMC
2025-01-01
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| Series: | BMC Pregnancy and Childbirth |
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| Online Access: | https://doi.org/10.1186/s12884-025-07143-9 |
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| author | Wei-jian Zeng Hua-jing Yang Ying-jie Gu Meng-nan Yang Meng-ru Sun Sheng-kai Cheng Yan-yan Hou Wei Gu |
| author_facet | Wei-jian Zeng Hua-jing Yang Ying-jie Gu Meng-nan Yang Meng-ru Sun Sheng-kai Cheng Yan-yan Hou Wei Gu |
| author_sort | Wei-jian Zeng |
| collection | DOAJ |
| description | Abstract Background Intrahepatic cholestasis of pregnancy (ICP) is the most common liver disorder associated with pregnancy and is usually diagnosed based on high serum bile acid. However, the pathogenesis of ICP is unclear. Ferroptosis has been reported as an iron-dependent mechanism of cell death. Although the role of Ferritin Heavy Chain 1 (FTH1) in ferroptosis has been extensively studied in various diseases, its mechanism in ICP through ferroptosis is yet to be analyzed. Methods Placental tissues from patients with ICP and healthy controls were employed to verify the expression of FTH1. Taurocholic acid (TCA)-induced HTR-8/SVneo cells were established as an in vitro model for ICP, and ferroptosis-related experiments were performed. In particular, HTR-8/SVneo cells with or without overexpressing FTH1 and HTR-8/SVneo cells with or without TCA induction were investigated to explore the relationship between FTH1 and ferroptosis during ICP in vitro, respectively. Results FTH1 was significantly downregulated in the ICP group compared with the control group. Furthermore, FTH1 and ferroptosis-related protein levels were downregulated, while the intracellular iron, reactive oxygen species, and lipid peroxidation levels were upregulated in the TCA-induced HTR-8/SVneo cells. In contrast, ferroptosis was inhibited by overexpression of FTH1 in TCA-induced HTR-8/SVneo cells. Conclusions A high concentration of TCA in HTR-8/SVneo cells decreased the expression of FTH1. Overexpression of FTH1 could prevent cell death from ferroptosis induced by TCA. Thus, inhibiting the downregulation of FTH1 could be a potential therapeutic target for ICP treatment. |
| format | Article |
| id | doaj-art-f93066ee320141cf9cb53e89f1e12d49 |
| institution | Kabale University |
| issn | 1471-2393 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Pregnancy and Childbirth |
| spelling | doaj-art-f93066ee320141cf9cb53e89f1e12d492025-01-12T12:43:43ZengBMCBMC Pregnancy and Childbirth1471-23932025-01-0125111310.1186/s12884-025-07143-9High taurocholic acid concentration induces ferroptosis by downregulating FTH1 expression in intrahepatic cholestasis of pregnancyWei-jian Zeng0Hua-jing Yang1Ying-jie Gu2Meng-nan Yang3Meng-ru Sun4Sheng-kai Cheng5Yan-yan Hou6Wei Gu7School of Medicine, The International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong UniversitySchool of Medicine, The International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong UniversitySchool of Medicine, The International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong UniversitySchool of Medicine, The International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong UniversitySchool of Medicine, The International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong UniversitySchool of Medicine, The International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong UniversitySchool of Medicine, The International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong UniversitySchool of Medicine, The International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong UniversityAbstract Background Intrahepatic cholestasis of pregnancy (ICP) is the most common liver disorder associated with pregnancy and is usually diagnosed based on high serum bile acid. However, the pathogenesis of ICP is unclear. Ferroptosis has been reported as an iron-dependent mechanism of cell death. Although the role of Ferritin Heavy Chain 1 (FTH1) in ferroptosis has been extensively studied in various diseases, its mechanism in ICP through ferroptosis is yet to be analyzed. Methods Placental tissues from patients with ICP and healthy controls were employed to verify the expression of FTH1. Taurocholic acid (TCA)-induced HTR-8/SVneo cells were established as an in vitro model for ICP, and ferroptosis-related experiments were performed. In particular, HTR-8/SVneo cells with or without overexpressing FTH1 and HTR-8/SVneo cells with or without TCA induction were investigated to explore the relationship between FTH1 and ferroptosis during ICP in vitro, respectively. Results FTH1 was significantly downregulated in the ICP group compared with the control group. Furthermore, FTH1 and ferroptosis-related protein levels were downregulated, while the intracellular iron, reactive oxygen species, and lipid peroxidation levels were upregulated in the TCA-induced HTR-8/SVneo cells. In contrast, ferroptosis was inhibited by overexpression of FTH1 in TCA-induced HTR-8/SVneo cells. Conclusions A high concentration of TCA in HTR-8/SVneo cells decreased the expression of FTH1. Overexpression of FTH1 could prevent cell death from ferroptosis induced by TCA. Thus, inhibiting the downregulation of FTH1 could be a potential therapeutic target for ICP treatment.https://doi.org/10.1186/s12884-025-07143-9FerroptosisFTH1Intrahepatic cholestasis of pregnancyPlacentaTaurocholic acid |
| spellingShingle | Wei-jian Zeng Hua-jing Yang Ying-jie Gu Meng-nan Yang Meng-ru Sun Sheng-kai Cheng Yan-yan Hou Wei Gu High taurocholic acid concentration induces ferroptosis by downregulating FTH1 expression in intrahepatic cholestasis of pregnancy BMC Pregnancy and Childbirth Ferroptosis FTH1 Intrahepatic cholestasis of pregnancy Placenta Taurocholic acid |
| title | High taurocholic acid concentration induces ferroptosis by downregulating FTH1 expression in intrahepatic cholestasis of pregnancy |
| title_full | High taurocholic acid concentration induces ferroptosis by downregulating FTH1 expression in intrahepatic cholestasis of pregnancy |
| title_fullStr | High taurocholic acid concentration induces ferroptosis by downregulating FTH1 expression in intrahepatic cholestasis of pregnancy |
| title_full_unstemmed | High taurocholic acid concentration induces ferroptosis by downregulating FTH1 expression in intrahepatic cholestasis of pregnancy |
| title_short | High taurocholic acid concentration induces ferroptosis by downregulating FTH1 expression in intrahepatic cholestasis of pregnancy |
| title_sort | high taurocholic acid concentration induces ferroptosis by downregulating fth1 expression in intrahepatic cholestasis of pregnancy |
| topic | Ferroptosis FTH1 Intrahepatic cholestasis of pregnancy Placenta Taurocholic acid |
| url | https://doi.org/10.1186/s12884-025-07143-9 |
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