Department of Obstetrics and Gynecology, The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Yuzhong, Chongqing, 400016, China.
Chongqing Key Laboratory of Maternal and Fetal Medicine, Chongqing, 400016, China.
Sci Rep. 2021 Oct 14;11(1):20469. doi: 10.1038/s41598-021-99837-1.
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.
子痫前期（PE）是一种严重的多系统妊娠并发症，其特征是妊娠高血压和蛋白尿。Bcl-2/腺病毒 E1B 19kDa 相互作用蛋白 3（BNIP3）是一种线粒体自噬的介质，已被证明与 PE 有关，但机制尚不清楚。本研究旨在探讨 BNIP3 在 PE 中的作用。通过 Western blot 和透射电子显微镜分析子痫前期和正常妊娠的胎盘，以定量 BNIP3 表达水平并观察细胞器形态。通过 Western blot、免疫荧光、流式细胞术、迁移和侵袭实验分析 BNIP3 敲低的滋养细胞。PE 患者的 BNIP3 表达受到抑制。与正常胎盘相比，PE 胎盘观察到自噬受损和线粒体损伤增加。BNIP3 抑制可抑制 Beclin-1 表达并减少 LC3-I 向 LC3-II 的转化。在 BNIP3 敲低组中，p62 过表达，氧化应激条件下 ROS 积累，凋亡过程升高。BNIP3 的敲低减少了 GFP-LC3 和线粒体的共定位。这项研究的结果表明，BNIP3 失调与 PE 中的线粒体自噬受损、氧化应激和细胞凋亡有关。该研究为 BNIP3 在 PE 病理生理学中的作用提供了新的见解。
