Pharmazentrum Frankfurt, Institut für Allgemeine Pharmakologie und Toxikologie/ZAFES, Klinikum der JW Goethe-Universität Frankfurt am Main, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany.
Curr Opin Pharmacol. 2010 Apr;10(2):185-90. doi: 10.1016/j.coph.2009.11.007. Epub 2010 Jan 4.
Extracellular matrix (ECM) components, commonly thought to function purely as structural elements are now demonstrated to act as signaling molecules. With the identification of matrix-derived endogenous ligands of Toll-like and NOD-like receptors of innate immunity, a general question about the mechanisms of soluble ECM components signaling as autonomous triggers of sterile or enhancers of pathogen-mediated inflammation gained notable relevance. They act as fundamental danger signals signifying tissue injury by eliciting a robust proinflammatory response. Immense therapeutic potential resides in translating this knowledge into the development of Toll-like and NOD-like receptor inhibitors. This review focuses on the role of ECM-derived ligands of innate immunity receptors as mediators of renal inflammation and promising pharmacological targets in kidney disease.
细胞外基质(ECM)成分通常被认为仅作为结构元件发挥作用,但现在已证明其可作为信号分子发挥作用。随着先天免疫 Toll 样和 NOD 样受体的基质衍生内源性配体的鉴定,一个关于可溶性 ECM 成分作为无菌或增强病原体介导炎症的自主触发物的信号转导机制的一般问题引起了人们的关注。它们作为基本危险信号,通过引发强烈的促炎反应来表示组织损伤。将这些知识转化为 Toll 样和 NOD 样受体抑制剂的开发,具有巨大的治疗潜力。这篇综述重点介绍了先天免疫受体的 ECM 衍生配体作为肾脏炎症的介质和肾脏疾病中有前途的药理靶点的作用。