化学基因CCL20通过调节OLR1表达来促进在代谢功能障碍相关的脂肪肝炎期间肝细胞胆固醇沉积,通过调节OLR1表达
Min Yin1, Yan Zhang2, Suosi Liu2
1National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology, Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China; Department of Clinical Nutrition, The Second Xiangya Hospital of Central South University, Changsha, China.
Metabolism: clinical and experimental
|May 28, 2025
概括
代谢功能障碍相关的脂肪肝炎 (MASH) 涉及增加的CCL20,主要来自肝脏前代细胞. 针对CCL20-CCR6-JNK-OLR1通路可以治疗MASH.
科学领域:
- 肝病学 肝病学是一种肝病学.
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
背景情况:
- 代谢功能障碍相关的脂肪肝炎 (MASH) 是肝脏疾病和移植的日益严重的原因.
- 驱动MASH病变的精确分子机制尚未完全理解.
研究的目的:
- 为了研究化学基因 (C-C 基因) 配体20 (CCL20) 在MASH的进展中的作用.
- 阐明CCL20影响MASH发育的分子途径.
主要方法:
- 使用RNA测序对人类和小鼠MASH肝脏组织中CCL20表达的分析.
- 使用肝脏CCL20-knockdown和肝脏原生细胞 (HPC) /胆管细胞特异性CCL20-knockout小鼠模型.
- 采用了体外和体内功能增加和丧失的研究来探索机制.
主要成果:
- 在MASH肝脏中,CCL20显著上调,与疾病严重程度相关.
- 由HPCs/胆细胞产生的CCL20,并由RELB/SOX9激活,驱动MASH病理.
- CCL20通过CCR6激活JNK通路,增加OLR1并促进胆固醇在肝细胞中的沉积.
结论:
- 在MASH进展中,CCL20-CCR6-JNK-OLR1轴至关重要.
- 抑制CCL20是一种有前途的MASH治疗策略.
相关概念视频
Cholesterol: Significance and Regulation
700
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...
700
Lipid Catabolism
180
Triglycerides serve as crucial long-term energy storage molecules in microorganisms, providing a dense source of metabolic energy. Their breakdown is mediated by lipases, which hydrolyze triglycerides into glycerol and free fatty acids. Each of these components follows distinct metabolic pathways, ultimately contributing to ATP synthesis and cellular energy homeostasis.Glycerol MetabolismGlycerol, released from triglyceride hydrolysis, is phosphorylated by glycerol kinase to form...
180
Cell Specific Gene Expression
14.0K
Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
14.0K
Liver Regeneration
3.4K
The liver is an important organ in vertebrates that plays an essential role in metabolism. It is also responsible for storing and redistributing nutrients such as carbohydrates, fats, and vitamins in the body. Additionally, the liver releases bile salts which are critical for digesting food and eliminating toxic metabolites from the body.
Cells of Liver
The liver comprises four major types of cells— hepatocytes, stellate, Kupffer, and sinusoidal endothelial cells. The hepatocytes are...
Cells of Liver
The liver comprises four major types of cells— hepatocytes, stellate, Kupffer, and sinusoidal endothelial cells. The hepatocytes are...
3.4K
Regulation of Nuclear Protein Sorting
2.4K
Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
2.4K
Liver Physiology
1.3K
The liver, an essential organ in the human body, performs over 200 vital functions that can be broadly categorized into metabolic, hematological, endocrine regulation, and bile production.
Metabolic Regulation:
The liver is the central organ involved in regulating blood composition. It stabilizes blood glucose levels, maintaining them within the range of 70–110 mg/dL. When these levels drop, the liver breaks down glycogen reserves and releases glucose into the bloodstream. It can...
Metabolic Regulation:
The liver is the central organ involved in regulating blood composition. It stabilizes blood glucose levels, maintaining them within the range of 70–110 mg/dL. When these levels drop, the liver breaks down glycogen reserves and releases glucose into the bloodstream. It can...
1.3K


