Toll-like receptor 4 signaling in liver injury and hepatic fibrogenesis.
Toll-like receptor 4 signaling in liver injury and hepatic fibrogenesis.
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Toll 样受体 4 信号在肝损伤和肝纤维化中的作用
DOI：
10.1186/1755-1536-3-21
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发表时间：
2010-10-21
期刊：
影响因子：
--
通讯作者：
Friedman SL
中科院分区：
文献类型：
--
作者：
Guo J;Friedman SL
toll样受体（TLRs）是一个跨膜模式识别受体（PRR）家族，通过识别细菌、真菌和病毒特有的结构成分，在先天免疫和适应性免疫中发挥关键作用。TLR4是研究最多的tlr，其主要外源配体是脂多糖，是革兰氏阴性菌壁的一种成分。在缺乏外源微生物的情况下，内源性配体，包括来自受损基质和受损细胞的损伤相关分子模式分子，也可以激活TLR4信号。在人类中，tlr4基因的单核苷酸多态性对其信号转导和包括肝硬化在内的特定疾病的相关风险有影响。在肝脏中，TLR4在所有实质细胞和非实质细胞类型中表达，并参与多种病因引起的组织损伤。完整的TLR4信号在肝星状细胞（HSCs）中被发现，HSCs是损伤肝脏中主要的纤维化细胞类型，并介导包括炎症表型、纤维化和抗凋亡特性在内的关键反应。进一步阐明hsc和其他肝细胞中TLR4信号的功能和内源性配体，可以揭示纤维形成的新机制，促进治疗策略的发展。
Toll-like receptors (TLRs) are a family of transmembrane pattern recognition receptors (PRR) that play a key role in innate and adaptive immunity by recognizing structural components unique to bacteria, fungi and viruses. TLR4 is the most studied of the TLRs, and its primary exogenous ligand is lipopolysaccharide, a component of Gram-negative bacterial walls. In the absence of exogenous microbes, endogenous ligands including damage-associated molecular pattern molecules from damaged matrix and injured cells can also activate TLR4 signaling. In humans, single nucleotide polymorphisms of theTLR4gene have an effect on its signal transduction and on associated risks of specific diseases, including cirrhosis. In liver, TLR4 is expressed by all parenchymal and non-parenchymal cell types, and contributes to tissue damage caused by a variety of etiologies. Intact TLR4 signaling was identified in hepatic stellate cells (HSCs), the major fibrogenic cell type in injured liver, and mediates key responses including an inflammatory phenotype, fibrogenesis and anti-apoptotic properties. Further clarification of the function and endogenous ligands of TLR4 signaling in HSCs and other liver cells could uncover novel mechanisms of fibrogenesis and facilitate the development of therapeutic strategies.