Extracellular matrix molecules: endogenous danger signals as new drug targets in kidney diseases.
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.
Schaefer
Liliana
L
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. Schaefer@med.uni-frankfurt.de
D000818:Animals; D016503:Drug Delivery Systems / Q000379:methods*; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D006801:Humans; D007113:Immunity, Innate; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000378:metabolism; D007674:Kidney Diseases / Q000188:drug therapy* / Q000378:metabolism; D009393:Nephritis / Q000188:drug therapy* / Q000378:metabolism; D053472:Nod Signaling Adaptor Proteins / Q000187:drug effects / Q000378:metabolism; D011509:Proteoglycans / Q000378:metabolism; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000187:drug effects / Q000378:metabolism
D016326:Extracellular Matrix Proteins; D018836:Inflammation Mediators; D053472:Nod Signaling Adaptor Proteins; D011509:Proteoglycans; D051193:Toll-Like Receptors