细胞外矩阵蛋白1与结缔组织生长因子结合,防止肝纤维化和状反应
Chunbao Sun1, Weiguo Fan2, Sreenivasulu Basha1
1Department of Pathology, Tulane University, New Orleans, Louisiana, USA.
Hepatology communications
|October 29, 2024
概括
细胞外矩阵蛋白1 (ECM1) 结合结缔组织生长因子 (CTGF),抑制TGFβ激活并减少肝纤维化. 向ECM1损失为慢性肝病 (如胆血管病和酒精相关肝病 (ALD)) 提供了潜在的治疗方法.
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
- 生物化学 生物化学
背景情况:
- 已知细胞外矩阵蛋白1 (ECM1) 抑制TGFβ激活.
- 尚不清楚ECM1的抗纤维作用,特别是其与结缔组织生长因子 (CTGF) 的相互作用.
研究的目的:
- 为了研究ECM1.1的功能.
- 检查ECM1和CTGF在肝纤维化和管状反应 (DR) 中的物理相互作用.
主要方法:
- 在接受肝纤维化和DR诱导 (DDC或ANIT养) 的动物中使用ECM1淘汰和过度表达模型.
- 在人类酒精相关性肝病 (ALD) 和模仿ALD的西方饮食诱导 (WDA) 模型中分析了ECM1和CTGF.
- 采用酵母双杂交系统和培养肝细胞来研究ECM1-CTGF相互作用.
主要成果:
- ECM1直接结合CTGF,抑制整合素αvβ6介导的TGFβ激活,并在体外减少纤维化.
- 在人类ALD中,ECM1下调与胆道CTGF诱导相关.
- 失去ECM1会加剧DDC诱导的肝损伤和纤维化,而过度表达ECM1会减轻DR和纤维化.
结论:
- 通过结合CTGF和抑制TGFβ激活,ECM1表现出一种新的抗纤维菌机制.
- ECM1的抗纤维素特性表明,在慢性疾病 (如胆道血管病变和ALD) 中,对管状反应和肝纤维化有治疗潜力.
相关概念视频
01:25Fibronectins Connect Cells with ECM
2.4K
Fibronectin is an adhesive glycoprotein present in the extracellular matrix of embryogenic and adult tissue. These molecules primarily aid in regulating cell motility and attachment. A fibronectin molecule is composed of two identical polypeptide chains attached to each other by a pair of disulfide bonds at the C-terminal.
Both proteoglycans and collagen are attached to fibronectin proteins, which, in turn, are attached to integrin proteins. These integrin proteins interact with transmembrane...
Both proteoglycans and collagen are attached to fibronectin proteins, which, in turn, are attached to integrin proteins. These integrin proteins interact with transmembrane...
2.4K
01:26Extracellular Matrix
2.8K
Unlike epithelial tissue, which is composed of cells closely packed with little or no extracellular space in between, connective tissue cells are dispersed in a matrix. This extracellular matrix (ECM) is composed of fibrous proteins like collagen, elastin, and fibronectin in a ground substance consisting of interstitial fluid, cell adhesion proteins, and proteoglycans. The proteoglycans form a gel-like material in the spaces between cells and provide hydration, buffering, binding, and force...
2.8K
01:42The Extracellular Matrix
81.5K
Overview
81.5K
01:13Cell-matrix's Response to Mechanical Forces
2.6K
In animal cells, the extracellular matrix allows cells within tissues to withstand external stresses and transmits signals from the outside of the cell to the inside. The extracellular matrix is extensive, and its composition varies between different types of tissues. For example, the reticular fibers and ground substance make up the ECM in loose connective tissue, while collagen and bone minerals make up the ECM of bone tissue.
Anchoring junctions mechanically attach a cell to the...
Anchoring junctions mechanically attach a cell to the...
2.6K
01:24Overview of Cell-Matrix Interactions
7.1K
The extracellular matrix or ECM holds cells together to form a tissue and allows the cells within the tissue to communicate. ECM comprises proteins such as fibronectin, collagen, laminin, etc. The most abundant protein in this space is collagen. Collagen fibers are interwoven with carbohydrate-containing protein molecules called proteoglycans. ECM allows cell migration and provides a structural scaffold at cell adhesion that anchors the cell when the extracellular matrix proteins interact with...
7.1K
01:09Introduction to Fibroblasts
3.0K
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...
3.0K