细胞外矩阵衍生损伤相关的分子模式 (DAMP):系统性硬化和纤维化方面的影响
Swarna Bale1, Priyanka Verma1, John Varga1
1Michigan Scleroderma Program, Division of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
The Journal of investigative dermatology
|July 15, 2023
概括
与损伤相关的分子模式 (DAMPs) 激活通关类受体 (TLRs),驱动系统性硬化症 (SSc) 中的纤维化. 针对这些DAMP为纤维性疾病提供了潜在的新疗法.
科学领域:
- 免疫学 免疫学 免疫学
- 纤维化研究 纤维化研究
- 自免疫性疾病 自免疫性疾病
背景情况:
- 与损伤相关的分子模式 (DAMPs) 是细胞应激或损伤期间释放的内源分子.
- 模式识别受体 (PRRs),包括收费类受体 (TLRs),识别DAMP,启动先天免疫反应.
- 系统性硬化症 (SSc) 是一种带有显著炎症的纤维性自身免疫性疾病.
研究的目的:
- 为了确定与全身性硬化症 (SSc) 相关的DAMP.
- 调查已识别的DAMP在SSc病变发生中的作用.
- 探索针对纤维化中的DAMPs的治疗策略.
主要方法:
- 在SSc皮肤和肺部活检中对DAMP进行了无偏见的调查.
- 分析DAMP激活TLR4在树皮细胞上的分析.
- 在纤维化和SSc.中对DAMP功能的审查.
主要成果:
- 在SSc中,含有纤维素素的额外域A和田素C被确定为高度上调的DAMP.
- 这些DAMP激活TLR4,促进profibrotic反应和肌纤维细胞激活.
- 持续激活导致SSc.中的渐进性纤维化.
结论:
- 特定的DAMP对SSc的进展做出了重大贡献.
- 准DAMP-TLR4相互作用可能为SSc.提供治疗效益.
- 了解DAMP对于管理纤维性疾病至关重要.
相关概念视频
Extracellular Matrix
3.0K
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...
3.0K
The Extracellular Matrix
9.1K
Overview
In order to maintain tissue organization, many animal cells are surrounded by structural molecules that make up the extracellular matrix (ECM). Together, the molecules in the ECM maintain the structural integrity of tissue as well as the remarkable specific properties of certain tissues.
Composition of the Extracellular Matrix
The extracellular matrix (ECM) is commonly composed of ground substance, a gel-like fluid, fibrous components, and many structurally and functionally diverse...
In order to maintain tissue organization, many animal cells are surrounded by structural molecules that make up the extracellular matrix (ECM). Together, the molecules in the ECM maintain the structural integrity of tissue as well as the remarkable specific properties of certain tissues.
Composition of the Extracellular Matrix
The extracellular matrix (ECM) is commonly composed of ground substance, a gel-like fluid, fibrous components, and many structurally and functionally diverse...
9.1K
Cell-matrix's Response to Mechanical Forces
2.7K
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...
2.7K
Role of Matrix Metalloproteases in Degradation of ECM
2.4K
Matrix metalloproteases (MMPs) are enzymes involved in the hydrolysis of proteins and glycoproteins of the extracellular matrix. MMPs are essential for the migration and proliferation of cells through the dense matrix network, throughout embryonic development, and throughout morphogenesis. The first MMP activity discovered was a collagenase in a tadpole's tail undergoing metamorphosis. The active collagen deposition and modifications lead to the morphogenesis of tadpoles into the adult...
2.4K
Overview of Cell-Matrix Interactions
7.3K
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...
7.3K
Fibril-associated Collagen
2.6K
Fibril-associated collagens are a type of collagens present in the extracellular matrix with interrupted triple helices or FACIT (Fibril-associated collagens interrupted triple-helices). FACIT help connect and attach the collagen fibrils with each other as well as with other proteins of the extracellular matrix.
For example, the type II collagen fibrils in cartilage have covalently bound type IX fibril-associated collagens at regular intervals. Other types of fibril-associated collagens are...
For example, the type II collagen fibrils in cartilage have covalently bound type IX fibril-associated collagens at regular intervals. Other types of fibril-associated collagens are...
2.6K


