The Nucleotide Oligomerization Domain-Like Receptors in Kidney Injury

Abstract

Background: Inflammation is a hallmark of almost all forms of renal injury and the activation of the innate immune system is of importance in the development of many kidney diseases. Pattern recognition receptors (PRRs) act as sensors of the innate immune system to detect pathogen- or damage-associated molecular patterns, which initiate immune responses to resolve infections and repair damaged tissues. Abnormalities in PRR activation will lead to excessive inflammation.

Summary: Nucleotide oligomerization domain (NOD)-like receptors (NLRs) are recently identified intracellular PRRs that are essential to innate immune responses and tissue homeostasis. A better understanding of the function of NLRs will provide unexpected opportunities to develop new therapies for kidney diseases by modulation of the innate immune system.

Key messages: NLRs are constitutively expressed in the kidney and emerging evidence has shown that activation of NLRs plays an important role in the pathogenesis of renal injury. Among NLRs, NOD2 and NLRP3 inflammasome are the best characterized members in the kidney. In this review, we summarize current knowledge about the pathological mechanisms that are related to NOD2 and NLRP3 inflammasome in various kidney diseases by their canonical and non-canonical effects and discuss the opportunities of pharmacological targeting of NLR-mediated signaling pathways at multiple levels for the treatment of renal disease.

Keywords: Inflammation; Kidney disease; NLRP3; NOD2; Pattern recognition receptors.

Fig. 1

Classification and molecular structures of NLRs. AD = Activator domain; BIR = baculovirus inhibitor of an apoptosis protein repeat; FIIND = function to find domain; LRR = leucine-rich repeat; NACHT = NAIP (neuronal apoptosis inhibitor protein), C2TA (MHC class 2 transcription activator), HET-E (incompatibility locus protein from Podospora anserina) and TP1 (telomerase-associated protein); NAD = NACHT-associated domain.

Fig. 2

Summarized recent findings on the role of NOD2 and its canonical and non-canonical effects in kidney injury.

Fig. 3

Summarized recent findings on the function, activation and canonical and non-canonical effects of NLRP3 in kidney injury. EMT = Epithelial-mesenchymal transition.