Extracellular matrix molecules: endogenous danger signals as new drug targets in kidney diseases

Curr Opin Pharmacol. 2010 Apr;10(2):185-90. doi: 10.1016/j.coph.2009.11.007. Epub 2010 Jan 4.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Drug Delivery Systems / methods*
  • Extracellular Matrix Proteins / metabolism*
  • Humans
  • Immunity, Innate
  • Inflammation Mediators / antagonists & inhibitors
  • Inflammation Mediators / metabolism
  • Kidney Diseases / drug therapy*
  • Kidney Diseases / metabolism
  • Nephritis / drug therapy*
  • Nephritis / metabolism
  • Nod Signaling Adaptor Proteins / drug effects
  • Nod Signaling Adaptor Proteins / metabolism
  • Proteoglycans / metabolism
  • Signal Transduction
  • Toll-Like Receptors / drug effects
  • Toll-Like Receptors / metabolism

Substances

  • Extracellular Matrix Proteins
  • Inflammation Mediators
  • Nod Signaling Adaptor Proteins
  • Proteoglycans
  • Toll-Like Receptors