ATF7-PINK1轴在性结肠炎中控制菌和肠炎
Yidong Chen1,2, Xiaopeng Zhang1, Junrong Li1
1Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
概括
激活转录因子7 (ATF7) 通过PINK1调节菌,为性结肠炎 (UC) 提供潜在的治疗标. 降低ATF7与UC严重程度相关,影响肠道上皮细胞亡和炎症.
科学领域:
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
- 胃肠病学 胃肠病学
背景情况:
- 性结肠炎 (UC) 涉及慢性肠道炎症和上皮细胞死亡.
- 活化转录因子 (ATF) 在UC病变发生中的作用尚未完全理解.
- 线粒体,受损线粒体的选择性降解,对于细胞健康至关重要.
研究的目的:
- 研究ATF家族成员在性结肠炎中的表达和功能.
- 确定ATF7在调节线粒细胞衰变中的作用及其对UC进展的影响.
- 探索ATF7-PINK1轴作为UC的潜在治疗点.
主要方法:
- 量化PCR测量UC患者和对照中的ATF1-ATF7表达.
- 特定于IEC的ATF7淘汰赛小鼠模型和人类结肠上皮细胞.
- ChIP-seq,双化酶试验,电子显微镜和免疫光学来研究菌.
主要成果:
- 在UC患者中,ATF7的表达显著降低,与疾病严重程度 (梅奥得分) 相反相关.
- ATF7直接激活PINK1的转录,这是一个关键的线粒调节器.
- 丢失ATF7或PINK1会损害线粒体,增加线粒体功能障碍,上皮细胞亡和结肠炎症.
结论:
- 一个关键的ATF7-PINK1信号通路控制了线粒并减轻了UC的进展.
- 减少ATF7表达会通过破坏线粒和促进炎症而加剧UC.
- ATF7-PINK1轴代表了性结肠炎的一个有前途的治疗标.
关键词:
ATF7 ATF7 ATF7 ATF7 ATF7 ATF7 ATF7 ATF7 ATF7 ATF7 ATF7 ATF7标签:PINK1PINK1PINK1PINK1PINK1线粒细胞衰变 (mitophagy) 是一种神经衰变的过程.性结肠炎是一种更多相关视频
10:21Mechanistic Insight into the Development of TNBS-Mediated Intestinal Fibrosis and Evaluating the Inhibitory Effects of Rapamycin
Published on: September 12, 2019
7.3K
07:05Fluorescence-mediated Tomography for the Detection and Quantification of Macrophage-related Murine Intestinal Inflammation
Published on: December 15, 2017
8.4K
相关概念视频
01:27Inflammatory Bowel Disease I: Ulcerative Colitis
342
Introduction
Inflammatory bowel disease, or IBD, encompasses a group of disorders characterized by chronic inflammation or ulceration of the gastrointestinal tract.
Risk Factors
The exact cause of IBD remains unclear, although it is believed to be due to a mix of genetic, environmental, microbial, and immune factors. Genetic factors are significant in determining susceptibility to IBD, with family history being a critical risk factor. Individuals with a first-degree relative who has IBD are at...
Inflammatory bowel disease, or IBD, encompasses a group of disorders characterized by chronic inflammation or ulceration of the gastrointestinal tract.
Risk Factors
The exact cause of IBD remains unclear, although it is believed to be due to a mix of genetic, environmental, microbial, and immune factors. Genetic factors are significant in determining susceptibility to IBD, with family history being a critical risk factor. Individuals with a first-degree relative who has IBD are at...
342
01:37The Unfolded Protein Response
5.1K
The ER is the hub of protein synthesis in a cell. It has robust systems to quality control protein folding and also for degradation of terminally misfolded proteins. Under normal conditions, a small proportion of misfolded proteins that cannot be salvaged need to be transported to the cytoplasm by the ER-associated degradation or ERAD pathways. However, if the ERAD cannot handle the misfolded proteins, the cell activates the unfolded protein response or UPR to adjust the protein folding...
5.1K
01:19Translocation of Proteins into the Mitochondria
3.8K
Mitochondrial precursors are translocated to the internal subcompartments via independent mechanisms involving distinct protein machineries called translocases.
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
3.8K
01:29Drugs for Treatment of Ulcerative Colitis in IBD
243
Ulcerative colitis is a chronic inflammatory condition primarily affecting the colon and rectum. The primary drugs used in the treatment of ulcerative colitis are aminosalicylates. They exhibit anti-inflammatory and immunosuppressive properties. They modulate inflammatory mediators and inhibit the activity of nuclear factor κB (NF-κB). Aminosalicylates also reduce inflammation by inhibiting prostaglandin and leukotriene production and decreasing neutrophil chemotaxis and superoxide...
243
01:12Role Of Notch Signalling In Intestinal Stem Cell Renewal
2.2K
Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
2.2K
01:31Regulation of the Unfolded Protein Response
2.6K
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...
2.6K