瘦素作为器官纤维化的一个关键驱动器
Xue-Nan Sun1, Shiuhwei Chen1, Shangang Zhao1,2
1Touchstone Diabetes Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Science advances
|October 22, 2025
概括
用新型抗体中和瘦素显著减少了小鼠在多个器官中的纤维化. 这种抗体阻断了瘦素信号传递,为纤维性疾病提供了潜在的新疗法.
科学领域:
- 生物化学 生物化学
- 免疫学 免疫学 免疫学
- 病理学 病理学 病理学
背景情况:
- 瘦素是一种脂肪细胞中的激素,调节新陈代谢和能量平衡.
- 莱普信号越来越多地与组织纤维化的发展有关.
- 瘦素受体 (LEPR) 调解瘦素的生物效应.
研究的目的:
- 阐明勒素中和抗体 (hLep3) 与勒素相互作用的结构基础.
- 在纤维化的临床前模型中评估hLep3的治疗疗效.
- 探索丁信号在纤维化病原发生中的机械作用.
主要方法:
- 使用X射线结晶学来确定hLep3未结合的结构和与Lep3结合的结构.
- 使用多个器官纤维化 (脏,肝脏,肺,心脏,血管) 的小鼠模型来评估治疗潜力.
- 机理学研究的重点是炎症和益纤维菌通路.
主要成果:
- 抗体对瘦素的结合方式模仿了瘦素受体的结合方式,揭示了其中和机制.
- 在所有测试的小鼠模型中,通过hLep3治疗中和化勒素显著抑制了纤维化进展.
- 抑制勒丁活性被证明可以减少促炎和益纤维素信号传递.
结论:
- 莱普信号传递是各种组织纤维化的关键驱动因素.
- 一种瘦素中和抗体 (hLep3) 显示出治疗纤维性疾病的显著治疗潜力.
- 向瘦素为抗纤维性疗法提供了一个有希望的策略.
更多相关视频
08:41Novel In Vivo Micro-Computed Tomography Imaging Techniques for Assessing the Progression of Non-Alcoholic Fatty Liver Disease
Published on: March 24, 2023
1.7K
08:34Mechanism of Regulation of Adipocyte Numbers in Adult Organisms Through Differentiation and Apoptosis Homeostasis
Published on: June 3, 2016
15.7K
相关概念视频
Liver Regeneration
4.2K
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...
4.2K
Cell Specific Gene Expression
16.2K
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...
16.2K
Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal
2.6K
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.
2.6K
Introduction to Fibroblasts
3.8K
Rudolph Virchow discovered spindle-shaped cells called fibroblasts in 1858. Inactive fibroblasts, called fibrocytes, become activated by various stimuli, such as growth factors and inflammatory cytokines. Activated fibroblasts play a crucial role in wound healing, inflammation, formation of new blood vessels, and cancer progression. Uncontrolled activation of fibroblasts results in fibrosis, the excess deposition of fibrous tissue, which can lead to scarring and affect normal organs. This...
3.8K
Regulation of Angiogenesis and Blood Supply
3.3K
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
3.3K
