转录因子XBP1调节线粒体重塑和自性流产中的自性流产
Weihua He1, Yating Zhao1, Lijun Yin1
1Department of Gynecology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
International immunopharmacology
|March 11, 2025
概括
通过XBP1s抑制向内质网膜应激 (ERS) 显示了自发流产 (SA) 的治疗潜力. 这种方法恢复了线粒体功能,促进了自,为SA病原和治疗策略提供了新的见解.
科学领域:
- 生殖生物学 生殖生物学
- 细胞应激反应的细胞应激反应
- 线粒体动力学的动态
背景情况:
- 自发流产 (SA) 是怀孕早期的一个重大临床问题.
- 细胞内膜网膜应激 (ERS) 与妊娠并发症有关,但其在SA病原发生中的作用尚未完全理解.
- 乳功能障碍是早期妊娠损失的一个关键因素.
研究的目的:
- 调查ERS在SA中的机械作用.
- 探索针对SA.中与ERS相关的乳功能障碍的治疗潜力.
- 为了阐明XBP1s和TRAF6在ERS诱导的叶细胞损伤中的参与.
主要方法:
- 在使用突尼卡米辛 (Tu) 的决定性 stromal 细胞 (DSC) 和怀孕小鼠中建立了一个 ERS 模型.
- 使用ChIP和双化酶试验评估了XBP1s和TRAF6之间的相互作用.
- 在DSC和体内模型中对XBP1s抑制 (shXBP1或STF-083010) 的反应中评估线粒体功能,亡,炎症和自.
主要成果:
- 在SA患者和Tu治疗的DSC中观察到XBP1s的升级.
- 抑制XBP1s减弱了Tu诱导的亡和促炎性细胞因子的产生.
- 抑制XBP1s增强了线粒体膜潜力,并促进了自,通过TRAF6/mTORC2途径进行介导.
- 过度表达TRAF6加剧了线粒体功能障碍和亡,同时抑制了自.
结论:
- 抑制XBP1s可以恢复线粒体平衡,并在ERS条件下促进自.
- 调节TRAF6/mTORC2轴是XBP1s抑制的保护作用的关键机制.
- 准ERS通路,特别是XBP1s,为自发流产提供了一个有前途的治疗策略.
相关概念视频
The Intrinsic Apoptotic Pathway
5.9K
Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
5.9K
Autophagic Cell Death
2.9K
Christian de Duve discovered “autophagy,” a process in which cellular components are engulfed by membrane-bound organelles called autophagosomes. The autophagosomes then fuse with lysosomes to digest the enclosed contents. Autophagy is generally activated in cells to prevent cell death. However, cell death is triggered when the damage is beyond repair.
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and...
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and...
2.9K
Apoptosis
10.5K
Apoptosis is a combination of two Greek words, 'apo' and 'ptosis,' meaning separation and falling off, respectively. Hippocrates used this word to describe gangrene, which was caused due to bandaging of fractured bones. Apoptosis was distinguished from necrosis in 1970 when John Kerr reported observations of morphological changes occurring during apoptosis. During one experiment, he observed that the disruption of blood supply to the liver tissue resulted in a size...
10.5K
Regulation of the Unfolded Protein Response
2.4K
Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
2.4K
Abnormal Proliferation
4.4K
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.4K
The Extrinsic Apoptotic Pathway
5.8K
The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
5.8K


