相关实验视频
Updated: Jul 7, 2025

12:43
On-Chip Endothelial Inflammatory Phenotyping
Published on: July 21, 2012
10.9K
减少HRD1促进胆固醇诱导的血管光滑肌细胞通过内分泌网膜应激变化的表型变化
Linli Wang1, Zhitao Ren2, Lin Wu1
1Department of Cardiology, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510630, China.
Molecular and cellular biochemistry
|December 25, 2023
概括
蛋白质质量的关键调节者HRD1在动脉样硬化期间在血管光滑肌细胞中减少. 它的缺乏促进细胞变化,有助于血管重塑,并提供潜在的治疗点.
科学领域:
- 血管生物学 血管生物学
- 细胞的新陈代谢
- 动脉样硬化研究 动脉样硬化研究
背景情况:
- 血管光滑肌细胞 (VSMC) 现型变化驱动动动脉硬化中的病态血管重塑.
- 内质网膜 (ER) 通过蛋白质质量控制维持VSMC功能,与ER相关的降解 (ERAD) 对于清除错误折叠的蛋白质至关重要.
- HRD1是参与脂质代谢的关键ERAD调节器,但其在动脉样硬化期间在VSMC中的作用尚不清楚.
研究的目的:
- 在动脉样硬化血管改造的背景下,研究HRD1在VSMC中的功能.
- 确定HRD1缺陷对VSMC表型,增殖,迁移和ER压力的影响.
- 探索HRD1作为代谢障碍诱导的血管改造的潜在治疗点.
主要方法:
- 在高脂肪饮食 (HFD) 的小鼠大动脉组织中分析HRD1表达.
- 组织学染色 (H&E,EVG) 来评估血管变化.
- 免疫光学,西部斑点,伤口关闭,穿孔检测,CRISPR基因编辑和体外转录组分析.
- 胆固醇补充剂诱导VSMC表型变化和HRD1下调.
主要成果:
- 在食HFD和补充胆固醇的小鼠的大动脉组织中,HRD1的表达显著降低.
- 在VSMCs中HRD1缺乏导致了与ER压力,增殖和迁移相关的基因的表达增加,同时减少了收缩基因.
- HRD1的丧失加剧了胆固醇诱导的VSMC增殖,迁移和ROS生产,促进了脱差.
结论:
- HRD1通过负面调节ER压力,在维护VSMC收缩性平衡中发挥关键作用.
- 在VSMC中HRD1缺陷有助于与代谢障碍相关的血管重塑.
- 针对VSMC中的HRD1是一个潜在的动脉样硬化治疗策略.
相关概念视频
Smooth Endoplasmic Reticulum
5.8K
Smooth endoplasmic reticulum or smooth ER is a sub-organelle with specialized functions in animal cells and plant cells. It is often associated with the tubule morphology of the endoplasmic reticulum.
The ER provides optimal conditions for synthesizing steroid hormones and lipids, such as phospholipids and triglycerides. Traditionally, lipid metabolism was considered to be a smooth ER function. However, there is no direct evidence to prove that rough ER is completely excluded from lipid...
The ER provides optimal conditions for synthesizing steroid hormones and lipids, such as phospholipids and triglycerides. Traditionally, lipid metabolism was considered to be a smooth ER function. However, there is no direct evidence to prove that rough ER is completely excluded from lipid...
5.8K
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
Export of Misfolded Proteins out of the ER
3.6K
After folding, the ER assesses the quality of secretory and membrane proteins. The correctly folded proteins are cleared by the calnexin cycle for transport to their final destination, while misfolded proteins are held back in the ER lumen. The ER chaperones attempt to unfold and refold the misfolded proteins but sometimes fail to achieve the correct native conformation. Such terminally misfolded proteins are then exported to the cytosol by ER-associated degradation or ERAD pathway for...
3.6K
Cholesterol: Significance and Regulation
551
Although not a source of energy, cholesterol plays a significant role as a foundational structure for bile salts, steroid hormones, and vitamin D, as well as being a crucial component of plasma membranes. Approximately 15% of blood cholesterol is derived from our diet, with the remainder synthesized from acetyl CoA by the liver and intestines. Cholesterol is eliminated from the body through its conversion into bile salts, which are eventually discarded in the feces.
Considering cholesterol and...
Considering cholesterol and...
551
Role of ER in the Secretory Pathway
5.4K
Eukaryotic cells have a special pathway that enables communication between various intracellular membrane-bound compartments and also with the extracellular environment. This pathway is termed as the secretory pathway.
Components of the secretory pathway
About a third of proteins synthesized in the cell are sorted via the secretory route. They shuffle between different compartments in membrane-bound vesicles until they reach their final destination. The main intracellular compartments involved...
Components of the secretory pathway
About a third of proteins synthesized in the cell are sorted via the secretory route. They shuffle between different compartments in membrane-bound vesicles until they reach their final destination. The main intracellular compartments involved...
5.4K
The Unfolded Protein Response
4.6K
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...
4.6K

