Beyond tissue injury-damage-associated molecular patterns, toll-like receptors, and inflammasomes also drive regeneration and fibrosis.
Tissue injury initiates an inflammatory response through the actions of immunostimulatory molecules referred to as damage-associated molecular patterns (DAMPs). DAMPs encompass a group of heterogenous molecules, including intracellular molecules released during cell necrosis and molecules involved in extracellular matrix remodeling such as hyaluronan, biglycan, and fibronectin. Kidney-specific DAMPs include crystals and uromodulin released by renal tubular damage. DAMPs trigger innate immunity by activating Toll-like receptors, purinergic receptors, or the NLRP3 inflammasome. However, recent evidence revealed that DAMPs also trigger re-epithelialization upon kidney injury and contribute to epithelial-mesenchymal transition and, potentially, to myofibroblast differentiation and proliferation. Thus, these discoveries suggest that DAMPs drive not only immune injury but also kidney regeneration and renal scarring. Here, we review the data from these studies and discuss the increasingly complex connection between DAMPs and kidney diseases.
Nephrological Center, Medizinische Klinik und Poliklinik IV, University of Munich, Munich, Germany; and hjanders@med.uni-muenchen.de schaefer@med.uni-frankfurt.de.
Hans-Joachim
HJ
Anders
Pharmazentrum Frankfurt, Institute of General Pharmacology and Toxicology, Goethe-University of Frankfurt/Main, Frankfurt/Main, Germany hjanders@med.uni-muenchen.de schaefer@med.uni-frankfurt.de.
Liliana
L
Schaefer
D058186:Acute Kidney Injury / Q000276:immunology; D000818:Animals; D005355:Fibrosis / Q000276:immunology; D006801:Humans; D058847:Inflammasomes / Q000502:physiology*; D007249:Inflammation / Q000276:immunology*; D018836:Inflammation Mediators / Q000502:physiology*; D007668:Kidney / Q000293:injuries* / Q000473:pathology* / Q000502:physiology; D007674:Kidney Diseases / Q000276:immunology*; D012038:Regeneration / Q000502:physiology*; D051436:Renal Insufficiency, Chronic / Q000276:immunology; D051193:Toll-Like Receptors / Q000502:physiology*
D058847:Inflammasomes; D018836:Inflammation Mediators; D051193:Toll-Like Receptors
ARF; GN; immunology and pathology