miR-30-5p-mediated ferroptosis of trophoblasts is implicated in the pathogenesis of preeclampsia
Oxidative stress is a major cause of adverse outcomes in preeclampsia (PE). Ferroptosis, i.e. programmed cell death from iron-dependent lipid peroxidation, likely mediates PE pathogenesis. We evaluated specific markers for ferroptosis in normal and PE placental tissues, using in vitro (trophoblasts)...
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| Format: | Article |
| Language: | English |
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Elsevier
2020-01-01
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| Series: | Redox Biology |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S221323171930919X |
| _version_ | 1818338032466526208 |
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| author | Heng Zhang Yue He Jian-xia Wang Ming-hua Chen Jian-juan Xu Min-hui Jiang Ya-ling Feng Yan-fang Gu |
| author_facet | Heng Zhang Yue He Jian-xia Wang Ming-hua Chen Jian-juan Xu Min-hui Jiang Ya-ling Feng Yan-fang Gu |
| author_sort | Heng Zhang |
| collection | DOAJ |
| description | Oxidative stress is a major cause of adverse outcomes in preeclampsia (PE). Ferroptosis, i.e. programmed cell death from iron-dependent lipid peroxidation, likely mediates PE pathogenesis. We evaluated specific markers for ferroptosis in normal and PE placental tissues, using in vitro (trophoblasts) and in vivo (rat) models. Increase in malondialdehyde content and total Fe2+ along with reduced the glutathione content and glutathione peroxidase activity was observed in PE placenta. While the trophoblasts experienced death under hypoxia, inhibitors of ferroptosis, apoptosis, autophagy, and necrosis increased the cell viability. Microarrays, bioinformatic analysis, and luciferase reporter assay revealed that upregulation of miR-30b-5p in PE models plays a pivotal role in ferroptosis, by downregulating Cys2/glutamate antiporter and PAX3 and decreasing ferroportin 1 (an iron exporter) expression, resulting in decreased GSH and increased labile Fe2+. Inhibition of miR-30b-5p expression and supplementation with ferroptosis inhibitors attenuated the PE symptoms in rat models, making miR-30b-5p a potential therapeutic target for PE. Keywords: miR-30-5p, Ferroptosis, Preeclampsia, SLC7A11, Ferroportin 1 |
| first_indexed | 2024-12-13T15:04:40Z |
| format | Article |
| id | doaj.art-23dd51588ad14a33bec6325d8aec1b88 |
| institution | Directory Open Access Journal |
| issn | 2213-2317 |
| language | English |
| last_indexed | 2024-12-13T15:04:40Z |
| publishDate | 2020-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Redox Biology |
| spelling | doaj.art-23dd51588ad14a33bec6325d8aec1b882022-12-21T23:41:02ZengElsevierRedox Biology2213-23172020-01-0129miR-30-5p-mediated ferroptosis of trophoblasts is implicated in the pathogenesis of preeclampsiaHeng Zhang0Yue He1Jian-xia Wang2Ming-hua Chen3Jian-juan Xu4Min-hui Jiang5Ya-ling Feng6Yan-fang Gu7Department of Child Health Care, Wuxi Maternity and Child Health Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu Province, 214002, ChinaDepartment of Obstetrics and Gynecology, Wuxi Matemal and Child Health Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu Province, 214002, PR ChinaDepartment of Women Health Care, Wuxi Maternity and Child Health Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu Province, 214002, ChinaDepartment of Obstetrics and Gynecology, Wuxi Matemal and Child Health Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu Province, 214002, PR ChinaDepartment of Obstetrics and Gynecology, Wuxi Matemal and Child Health Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu Province, 214002, PR ChinaDepartment of Obstetrics and Gynecology, Wuxi Matemal and Child Health Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu Province, 214002, PR ChinaDepartment of Obstetrics and Gynecology, Wuxi Matemal and Child Health Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu Province, 214002, PR China; Corresponding author.Department of Obstetrics and Gynecology, Wuxi Matemal and Child Health Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu Province, 214002, PR ChinaOxidative stress is a major cause of adverse outcomes in preeclampsia (PE). Ferroptosis, i.e. programmed cell death from iron-dependent lipid peroxidation, likely mediates PE pathogenesis. We evaluated specific markers for ferroptosis in normal and PE placental tissues, using in vitro (trophoblasts) and in vivo (rat) models. Increase in malondialdehyde content and total Fe2+ along with reduced the glutathione content and glutathione peroxidase activity was observed in PE placenta. While the trophoblasts experienced death under hypoxia, inhibitors of ferroptosis, apoptosis, autophagy, and necrosis increased the cell viability. Microarrays, bioinformatic analysis, and luciferase reporter assay revealed that upregulation of miR-30b-5p in PE models plays a pivotal role in ferroptosis, by downregulating Cys2/glutamate antiporter and PAX3 and decreasing ferroportin 1 (an iron exporter) expression, resulting in decreased GSH and increased labile Fe2+. Inhibition of miR-30b-5p expression and supplementation with ferroptosis inhibitors attenuated the PE symptoms in rat models, making miR-30b-5p a potential therapeutic target for PE. Keywords: miR-30-5p, Ferroptosis, Preeclampsia, SLC7A11, Ferroportin 1http://www.sciencedirect.com/science/article/pii/S221323171930919X |
| spellingShingle | Heng Zhang Yue He Jian-xia Wang Ming-hua Chen Jian-juan Xu Min-hui Jiang Ya-ling Feng Yan-fang Gu miR-30-5p-mediated ferroptosis of trophoblasts is implicated in the pathogenesis of preeclampsia Redox Biology |
| title | miR-30-5p-mediated ferroptosis of trophoblasts is implicated in the pathogenesis of preeclampsia |
| title_full | miR-30-5p-mediated ferroptosis of trophoblasts is implicated in the pathogenesis of preeclampsia |
| title_fullStr | miR-30-5p-mediated ferroptosis of trophoblasts is implicated in the pathogenesis of preeclampsia |
| title_full_unstemmed | miR-30-5p-mediated ferroptosis of trophoblasts is implicated in the pathogenesis of preeclampsia |
| title_short | miR-30-5p-mediated ferroptosis of trophoblasts is implicated in the pathogenesis of preeclampsia |
| title_sort | mir 30 5p mediated ferroptosis of trophoblasts is implicated in the pathogenesis of preeclampsia |
| url | http://www.sciencedirect.com/science/article/pii/S221323171930919X |
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