Research Progress on the Role of Inflammasomes in Kidney Disease

Abstract

Inflammasomes are multimeric complexes composed of cytoplasmic sensors, apoptosis-associated speck-like protein containing a caspase activation and recruitment domain (ASC or PYCARD), and procaspase-1 and play roles in regulating caspase-dependent inflammation and cell death. Inflammasomes are assembled by sensing pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) and initiate inflammatory responses by activating caspase-1. Activated caspase-1 promotes the release of the inflammatory cytokines interleukin-1β (IL-1β) and IL-18 and eventually induces pyroptosis. Inflammasomes are closely related to kidney diseases. In particular, the NLRP3 (NACHT, LRR, and PYD domain-containing protein 3) inflammasome has been shown to cause acute and chronic kidney diseases by regulating canonical and noncanonical mechanisms of inflammation. Small-molecule inhibitors that target NLRP3 and other components of the inflammasome are potential options for the treatment of kidney-related diseases such as diabetic nephropathy. This article will focus on the research progress on inflammasomes and the key pathogenic roles of inflammasomes in the development and progression of kidney diseases and explore the potential of this intracellular inflammation to further prevent or block the development of the kidney disease.

Long non-coding RNA CDKN2B-AS1 regulates high glucose-induced human mesangial cell injury via regulating the miR-15b-5p/WNT2B axis

“…At present, conventional DN treatment measures include controlling blood sugar and blood pressure, and using inhibitors of the renin-angiotensin-aldosterone system, but this only slows the progression of DN without stopping or reversing it [5]. Studies have revealed that high glucose (HG) can induce mesangial cell ECM accumulation, proliferation, and inflammation response [6][7][8]. Hence, exploring the mechanisms that regulate the process of mesangial cells in DN is of great significance for the development of DN therapeutic strategies.…”

LncRNA‐HOTAIR promotes endothelial cell pyroptosis by regulating the miR‐22/NLRP3 axis in hyperuricaemia

“…In particular, the nucleotide-binding domain and leucine-rich repeat (NLR) protein 3 (NLRP3) inflammasome has been shown to cause acute and chronic kidney diseases by regulating canonical and non-canonical mechanisms of inflammation. [9][10][11] Therefore, the involvement of NLRP3 in kidney damage caused by high serum UA stimulation cannot be ignored in clinical practice. The NLRP3 inflammasome is composed of NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC) and active caspase-1, which regulates interleukin-1β (IL-1β) maturation.…”

Emerging Role of the Inflammasome and Pyroptosis in Hypertension

“…Enhanced NLRP3 expression was detected in murine cultured podocytes, and human kidneys with mild signs of diabetic nephropathy exhibited immunohistochemical staining for NLRP3 in proximal and distal tubules as well as in sporadic cells that appeared to be podocytes [ 148 ]. Moreover, the inhibition of the NLRP3 inflammasome ameliorates renal injury in a variety of animal models [ 149 ]. Taken together, all this accumulating evidence for the expression and activation of the NLRP3 inflammasome in different kidney cell types during kidney diseases strongly suggests a role for pyroptosis in hypertensive kidney disease.…”