Department of Obstetrics and Gynecology, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
The Chongqing Key Laboratory of Translational Medicine in Major Metabolic Diseases, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
Acta Biochim Biophys Sin (Shanghai). 2024 May 22;56(10):1446-1459. doi: 10.3724/abbs.2024065.
Autophagy dysregulation and Ca -induced mitochondrial dysfunction in trophoblast cells are proposed to contribute to preeclampsia (PE) development. FAM134B is identified as a receptor associated with endoplasmic reticulum autophagy (ER-phagy). In this study, the placentas of normal pregnant women and PE patients are collected and analyzed by immunohistochemistry, quantitative real-time PCR, and western blot analysis. The effects of ER-phagy are investigated in HTR8/SVneo cells. Significantly increased levels of FAM134B, inositol-1,4,5-triphosphate receptor type 1 (IP3R), calnexin, cleaved caspase 3 and cytochrome C are detected in the PE placenta and sodium nitroprusside (SNP)-treated HTR-8/SVneo cells. Overexpression of FAM134B in HTR-8/SVneo cells results in increased apoptosis, impaired invasion capacity, and diminished mitochondrial function, while an autophagy inhibitor improves mitochondrial performance. Excessive ER-phagy is also associated with an increased concentration of gamma linolenic acid. Our findings suggest that FAM134B contributes to trophoblast apoptosis by mediating ER-mitochondria Ca transfer through mitochondria-associated endoplasmic reticulum membranes (MAMs) and subsequent mitochondrial function, further enhancing our understanding of PE etiology.
自噬失调和 Ca 诱导的线粒体功能障碍被认为与子痫前期 (PE) 的发展有关。FAM134B 被鉴定为内质网自噬 (ER-phagy) 的受体。在这项研究中，通过免疫组织化学、定量实时 PCR 和 Western blot 分析收集和分析了正常孕妇和 PE 患者的胎盘。在 HTR8/SVneo 细胞中研究了 ER-phagy 的作用。在 PE 胎盘和硝普钠 (SNP) 处理的 HTR-8/SVneo 细胞中，检测到 FAM134B、肌醇 1,4,5-三磷酸受体 1 (IP3R)、钙连蛋白、裂解的 caspase 3 和细胞色素 C 的水平显著增加。在 HTR-8/SVneo 细胞中过表达 FAM134B 会导致细胞凋亡增加、侵袭能力受损和线粒体功能下降，而自噬抑制剂可改善线粒体功能。过度的 ER-phagy 也与 γ-亚麻酸浓度的增加有关。我们的研究结果表明，FAM134B 通过介导线粒体相关内质网膜 (MAMs) 上的 ER-线粒体 Ca 转移和随后的线粒体功能，导致滋养细胞凋亡，进一步加深了我们对 PE 病因的理解。
