SIRT1稳定β-TrCP1以抑制牛1表达,维护肠道上皮质完整性以缓解大肠炎
Liang Wang1, Jinsong Li2, Mingshan Jiang3
1Institute of Basic Medicine and Forensic Medicine, North Sichuan Medical College, Nanchong, China; Center of Growth, Metabolism and Aging, Key Laboratory of Bio-Resource and Eco-Environment, Ministry of Education, College of Life Sciences, Sichuan University, Chengdu, China.
概括
Sirtuin 1 (SIRT1) 对于保持肠道屏障完整性至关重要. 激活SIRT1可以通过保护细胞结节和降低肠道透性来预防炎症性肠病 (IBD).
科学领域:
- 胃肠病学 胃肠病学
- 分子生物学分子生物学
- 炎症研究 炎症研究
背景情况:
- 肠上皮质屏障功能障碍增加了透性,这是炎症性肠病 (IBD) 的关键因素.
- SIRT1,一种依赖NAD+的脱乙酶,在炎症和IBD病变发生过程中发挥作用.
研究的目的:
- 研究SIRT1在维护肠道上皮质屏障完整性方面的保护作用.
- 阐明SIRT1影响细胞细胞结合和肠道健康的潜在分子机制.
主要方法:
- 通过GEO和免疫组织化学分析了人类IBD样本中的SIRT1表达.
- 利用SIRT1转基因小鼠和德克斯硫酸盐 (DSS) 模拟大肠炎,评估表型,肠道透性和细胞因子表达.
- 检查了细胞结蛋白表达在细胞系中响应DSS或SIRT1敲击的反应.
- 研究了尼古丁胺胺 mononucleotide (NMN) 在DSS诱导的大肠炎的治疗潜力.
主要成果:
- 减少SIRT1表达与人类IBD相关.
- 转基因SIRT1小鼠表现出减弱的DSS诱导的大肠炎.
- 通过NMN激活SIRT1,改善了小鼠的屏障功能和大肠炎.
- DSS降低了SIRT1的调节,破坏了β-TrCP1的稳定,提高了Snail1的调节,降低了E-cadherin/Occludin/Claudin-1,增加了透性和炎症.
- SIRT1-β-TrCP1-Snail1-Occludin/Claudin-1/E-cadherin通路的改变与人类的IBD有关.
结论:
- SIRT1对于保持肠道上皮质屏障完整性至关重要.
- SIRT1调节β-TrCP1-Snail1-E-cadherin/Occludin/Claudin-1通路,以保持屏障功能的作用.
相关概念视频
01:12Role Of Notch Signalling In Intestinal Stem Cell Renewal
2.1K
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...
2.1K
01:23Renewal of Intestinal Stem Cells
2.6K
The intestinal epithelial lining rapidly renews every 4 to 5 days. The renewal is facilitated by intestinal stem cells (ISCs) located at the base of the crypt– a gland located at the bottom of each villus. ISCs divide asymmetrically to form new stem cells and progenitor daughter cells. The daughter cells are called transit-amplifying (TA) cells which move upwards along the crypt and either differentiate into absorptive cells– the enterocytes or secretory cells– including the...
2.6K
01:22Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal
2.2K
Erythropoietin-producing hepatocellular carcinoma receptor (Eph) and its ligand, Eph receptor-interacting protein (Ephrin) were first discovered in the human carcinoma cell line, hence the name. Ephrin-Eph interaction guides cells to reach their appropriate location in adult tissues. They also play an essential role in the immune system by helping in immune cell migration, adhesion, and activation. Based on their structure and function, Eph is divided into two classes — EphA and EphB.
2.2K
01:31Regulation 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