TMAO通过长非编码RNA高度高调的肝癌 (HULC) 促进代谢功能障碍相关的脂肪肝疾病 (MAFLD) 的发展
Mohammad Moradzad1,2, Mohammad Raman Moloudi3, Alina Abdollahi4
1Student Research Committee, Kurdistan University of Medical Sciences, Sanandaj, Iran.
Journal of diabetes and metabolic disorders
|June 2, 2025
概括
三甲基胺N氧化物 (TMAO) 通过调节HULC和P38MAPK信号来驱动与代谢功能障碍相关的脂肪肝疾病 (MAFLD). 减少TMAO可能通过肠道微生物组调节为MAFLD提供治疗策略.
科学领域:
- 肝病学 肝病学是一种肝病学.
- 分子生物学分子生物学
- 肠道微生物组研究研究
背景情况:
- 与代谢功能障碍相关的脂肪肝疾病 (MAFLD) 的发病与三甲基胺N氧化物 (TMAO) 有关.
- 通过TMAO促进MAFLD的精确分子机制仍然不完全理解.
- 研究长非编码RNA HULC在TMAO诱导的MAFLD中的作用至关重要.
研究的目的:
- 阐明TMAO在MAFLD发展中的分子机制.
- 为了确定TMAO是否通过HULC途径加剧MAFLD.
- 在细胞MAFLD模型中研究TMAO/HULC/P38MAPK轴.
主要方法:
- 建立基于HepG2细胞的MAFLD模型.
- 在CRISPR/Cas13系统中介的HULC.中断.
- 在HULC敲除前和之后,细胞暴露在不同度的TMAO中.
- 通过RT-qPCR进行基因表达分析.
- 使用Annexin V-FITC和PI染色进行亡评估.
主要成果:
- 在MAFLD细胞中,TMAO显著上调HULC和P38MAPK的表达 (P<0.05).
- 在HULC的淘汰中,取消了TMAO诱导的P38MAPK及其下游目标 (TNFα,IL-6,PNPLA3) 的变化.
- 在脂肪肝细胞模型中,TMAO治疗显著增加了细胞亡 (P < 0.05).
结论:
- 在MAFLD病变发生过程中,TMAO/HULC/P38MAPK轴起着关键作用.
- 这个轴通过调节炎症和纤维化相关基因来促进MAFLD.
- 针对TMAO,可能通过肠道微生物组调节,代表了MAFLD的有希望的治疗途径.
相关概念视频
02:39lncRNA - Long Non-coding RNAs
9.0K
In humans, more than 80% of the genome gets transcribed. However, only around 2% of the genome codes for proteins. The remaining part produces non-coding RNAs which includes ribosomal RNAs, transfer RNAs, telomerase RNAs, and regulatory RNAs, among other types. A large number of regulatory non-coding RNAs have been classified into two groups depending upon their length – small non-coding RNAs, such as microRNA, which are less than 200 nucleotides in length, and long non-coding RNA...
9.0K
01:24Overview of Lipid Metabolism
2.6K
Lipid metabolism is a crucial process in the human body that involves the synthesis and degradation of lipids. This process is essential for energy production, cell membrane formation, and hormone production, among other functions.
Lipolysis: The Breakdown of Lipids:
Lipolysis is the process of breaking down lipids, particularly triglycerides, into glycerol and fatty acids. This process typically occurs in the adipose tissue and is triggered by various hormones, including glucagon and...
Lipolysis: The Breakdown of Lipids:
Lipolysis is the process of breaking down lipids, particularly triglycerides, into glycerol and fatty acids. This process typically occurs in the adipose tissue and is triggered by various hormones, including glucagon and...
2.6K
01:13Formation of Muscle Fibers from Myoblasts
5.2K
De novo myogenesis, or the formation of muscle fibers, begins during the early embryonic stages. The skeletal muscle is formed from somites– blocks of embryonic cell layers. The somites are further divided into dermatomes, myotomes, sclerotomes, and syndetomes. Among these, the myotomes give rise to muscle fibers.
Muscle progenitor cells (MPCs) are formed from the myotomes. MPCs express genes that encode the transcription factors Pax3 and Pax7. Along with Pax 3/7, other transcription...
Muscle progenitor cells (MPCs) are formed from the myotomes. MPCs express genes that encode the transcription factors Pax3 and Pax7. Along with Pax 3/7, other transcription...
5.2K