Role of NLRP3 Inflammasomes for Rhabdomyolysis-induced Acute Kidney Injury
نویسندگان
چکیده
Rhabdomyolysis is one of the main causes of community-acquired acute kidney injury (AKI). Although inflammation is involved in the pathogenesis of rhabdomyolysis-induced AKI (RIAKI), little is known about the mechanism that triggers inflammation during RIAKI. Recent evidence has indicated that sterile inflammation triggered by tissue injury can be mediated through multiprotein complexes called the inflammasomes. Therefore, we investigated the role of NLRP3 inflammasomes in the pathogenesis of RIAKI using a glycerol-induced murine rhabdomyolysis model. Inflammasome-related molecules were upregulated in the kidney of RIAKI. Renal tubular injury and dysfunction preceded leukocyte infiltration into the kidney during the early phase of RIAKI, and they were markedly attenuated in mice deficient in NLRP3, ASC, caspase-1, and interleukin (IL)-1β compared with those in wild-type mice. No difference in leukocyte infiltration was observed between wild-type and NLRP3-deficient mice. Furthermore, NLRP3 deficiency strikingly suppressed the expression of renal injury markers and inflammatory cytokines and apoptosis of renal tubular cells. These results demonstrated that NLRP3 inflammasomes contribute to inflammation, apoptosis, and tissue injury during the early phase of RIAKI and provide new insights into the mechanism underlying the pathogenesis of RIAKI.
منابع مشابه
Wasp stings (Vespa affinis) induced acute kidney injury following rhabdomyolysis in a 25-year-old woman.
Wasp sting is a relatively common arthropod assault. This usually results in pain and mild allergic reactions, but sometimes may cause severe systemic reaction and multiorgan dysfunction including rhabdomyolysis, hemolysis, coagulopathy, hepatic, renal and cardiac complications. Along with several other pathomechanisms, rhabdomyolysis is a distinguished cause of acute kidney injury (AKI) in pa...
متن کاملThe Preventive Role of Pioglitazone in Glycerol-Induced Acute Kidney Injury in Rats during Two Different Treatment Periods
Background: Acute kidney injury is the most life-threatening complication of rhabdomyolysis. Glycerol is commonly used to induce this injury. The aim was to investigate the renoprotective effects of pioglitazone and the possible advantage of administering the drug for a longer period.Methods: Twenty-four male Albino Wistar rats were randomly divided into 4 groups (n=6/group): (A) control, (B) g...
متن کاملRole of acetaminophen in reducing risk of kidney injury from Rhabdomyolysis: A Narrative Review
Background: Rhabdomyolysis is a clinical syndrome that results in releasing myoglobin content from damaged muscle cells into circulation and often causes acute kidney injury (1). Different mechanisms are considered to be responsible in rhabdomyolysis and renal failure. However, free radical generation is the most important mechanism resulting in kidney injury. Thus, the effect ...
متن کاملMolecular mechanisms of crystal-related kidney inflammation and injury. Implications for cholesterol embolism, crystalline nephropathies and kidney stone disease.
Crystals are particles of endogenous inorganic or organic composition that can trigger kidney injury when deposited or formed inside the kidney. While decades of research have focused on the molecular mechanisms of solute supersaturation and crystal formation, the pathomechanisms of crystal-induced renal inflammation remain largely unknown. The recent discovery of the intracellular NLRP3 inflam...
متن کاملInflammasomes in the Pathophysiology of Kidney Diseases.
BACKGROUND The inflammasome is a complex of proteins in the cytoplasm that consists of three main components: a sensor protein (receptor), an adapter protein and caspase-1. Inflammasomes are the critical components of innate immunity and have been gradually recognized as a critical mediator in various autoimmune diseases; also, their role in chronic kidney disease and acute kidney injury has be...
متن کامل