Bmal1通过非正规的循环节通路调节血管化
Ming He1, Yong Sun2, Chengyun Tang2
1Department of Pathology (M.H.), The University of Alabama at Birmingham.
Arteriosclerosis, thrombosis, and vascular biology
|January 29, 2026
概括
核心昼夜蛋白Bmal1 (基本螺旋环螺旋ARNT类蛋白1) 通过上调Runx2.2,驱动糖尿病诱导的血管化. 准Bmal1为糖尿病血管疾病提供了一个新的治疗策略.
科学领域:
- 心血管生物学 心血管生物学
- 内分泌学 在内分泌学.
- 循环节律是指循环节律的节奏.
背景情况:
- 血管化是糖尿病中心血管并发症的重要原因.
- 糖尿病会破坏昼夜节律,但昼夜节律调节者在血管化中的作用尚不清楚.
- 血管光滑肌细胞 (SMC) 的骨质性重编程有助于血管化.
研究的目的:
- 研究核心昼夜蛋白Bmal1在糖尿病相关的血管化中的作用.
- 阐明Bmal1在糖尿病中影响血管化的分子机制.
主要方法:
- 在糖尿病小鼠的大动脉,人类糖尿病动脉和高葡萄糖暴露的SMC中检查了Bmal1表达.
- 产生的SMC特定的Bmal1淘汰赛小鼠和诱导糖尿病.
- 通过染和脉冲波速度评估血管化和刚性.
- 利用RNA测序,ChIP和CRISPR-Cas9来定义Bmal1的调节机制.
主要成果:
- 在高血糖症下,Bmal1在糖尿病动脉和SMC中被选择性上调.
- 特定于SMC的Bmal1缺失减轻了糖尿病引起的血管化和大动脉硬.
- Bmal1直接与Runx2促进体结合,通过非正规的昼夜通路增强其转录.
结论:
- 通过直接转录调节Runx2.2,Bmal1是糖尿病诱导的血管化的关键媒介.
- 这项研究揭示了Bmal1在血管疾病中的新型致病作用.
- 针对像Bmal1这样的失调的昼夜因素,可能为糖尿病血管并发症提供新的治疗途径.
相关概念视频
Circadian Rhythms and Gene Regulation
4.6K
The biological clock is involved in many aspects of regulating complex physiology in all animals. It was in 1935 when German zoologists, Hans Kalmus and Erwin Bünning, discovered the existence of circadian rhythm in Drosophila melanogaster. However, the internal molecular mechanisms behind the circadian clock remained a mystery until 1984, when Jeffrey C. Hall, Michael Rosbash, and Michael W. Young discovered the expression of the Per gene oscillating over a 24-hour cycle. In subsequent...
4.6K
GTPases and their Regulation
9.8K
Guanine nucleotide-binding proteins (G-proteins), also known as GTPases, are a superfamily of proteins that regulate many cellular processes, such as cell signaling, vesicular transport, and the regulation of cell shape and motility. Mutation or dysfunction of these proteins can lead to disease. There are around 40,000 known G-proteins that can broadly be classified into two groups ‒ small G-proteins consisting of a single domain and large multi-domain G-proteins.
Large G-proteins,...
Large G-proteins,...
9.8K
Seedless Vascular Plants
66.8K
Seedless Vascular Plants Were the First Tall Plants on Earth
66.8K
C4 Pathway and CAM
49.1K
Most plants use the C3 pathway for carbon fixation. However, some plants, such as sugar cane, corn, and cacti that grow in hot conditions, use alternative pathways to fix carbon and conserve energy loss due to photorespiration. Photorespiration is the process that occurs when the oxygen concentration is high. Under such conditions, the rubisco enzyme in the Calvin cycle binds O2 instead of CO2, which halts photosynthesis and consumes energy.
C4 Pathway
The C4 pathway is used by plants such as...
C4 Pathway
The C4 pathway is used by plants such as...
49.1K
Epigenetic Regulation
33.7K
Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
33.7K
Regulated Protein Degradation
8.8K
It is vital to regulate the activity of enzymatic as well as non-enzymatic proteins inside the cell. This can be achieved either through creating a balance between their rate of synthesis and degradation or regulating the intrinsic activity of the protein. Both these regulation mechanisms play an essential role in the normal functioning of cells.
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
8.8K


