Zhou, Xiaobo, Zhao, Xue, Zhou, Wei, Qi, Hongbo, Zhang, Hua, Han, Ting li and Baker, Philip (2021) Impaired placental mitophagy and oxidative stress are associated with dysregulated BNIP3 in preeclampsia. Scientific Reports, 11. ISSN 2045-2322
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Abstract
Preeclampsia (PE) is a severe multisystem pregnancy complication characterized by gestational hypertension and proteinuria. Bcl-2/adenovirus E1B 19-kDa interacting protein 3 (BNIP3) is a mediator of mitophagy and has been proven to be associated with PE, but the mechanism is not well understood. This study aimed to investigate the role of BNIP3 in PE. Placentae from preeclamptic and normal pregnancies were analyzed by western-blot and transmission electron microscopy to quantify the level of BNIP3 expression and observe the organelle morphologies. Trophoblast cells with knockdown BNIP3 were analyzed by western-blot, immunofluorescence, flow cytometry, migration and invasion assays. BNIP3 expression was suppressed in PE patients. Impaired autophagy and increased mitochondrial damage were observed in PE placentae when compared with normal placentae. Suppression of BNIP3 inhibited Beclin-1 expression and reduced the transformation of LC3-I to LC3-II. In the knockdown BNIP3 group, p62 was overexpressed, ROS accumulated and the apoptotic process was elevated under oxidative stress condition. The knockdown of BNIP3 reduced the colocalization of GFP-LC3 and mitochondria. The findings of this study suggest that dysregulated BNIP3 is associated with impaired mitophagy, oxidative stress, and apoptosis in PE. The study provides new insights into the role of BNIP3 in the pathophysiology of PE.
Item Type: | Article |
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Additional Information: | Data availability statement: All data generated or analysed during this study are included in this published article and its Supplementary Information files. Funding information: This work was supported by The National Natural Science Foundation of China (grant number: 81971406, 81771607, 81871185, 81961128004), The 111 Project (grant number: Yuwaizhuan (2016)32), The National Key Research and Development Program of Reproductive Health and Major Birth Defects Control and Prevention (grant number: 2016YFC1000407), The Chongqing Health Commission (grant number: 2017ZDXM008, 2018ZDXM024), and The Chongqing Science and Technology Commission (grant number: cstc2017jcyjBX0060, cstc2018jcyjAX0359) research grants. |
Uncontrolled Keywords: | general ,/dk/atira/pure/subjectarea/asjc/1000 |
Faculty \ School: | Faculty of Medicine and Health Sciences > Norwich Medical School |
Related URLs: | |
Depositing User: | LivePure Connector |
Date Deposited: | 07 May 2025 14:30 |
Last Modified: | 09 May 2025 09:30 |
URI: | https://ueaeprints.uea.ac.uk/id/eprint/99196 |
DOI: | 10.1038/s41598-021-99837-1 |
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