Abstract
Pigment nephropathy is an acute decline in renal function following the deposition of endogenous haem-containing proteins in the kidneys. Haem pigments such as myoglobin and haemoglobin are filtered by glomeruli and absorbed by the proximal tubules. They cause renal vasoconstriction, tubular obstruction, increased oxidative stress and inflammation. Haem is associated with inflammation in sterile and infectious conditions, contributing to the pathogenesis of many disorders such as rhabdomyolysis and haemolytic diseases. In fact, haem appears to be a signalling molecule that is able to activate the inflammasome pathway. Recent studies highlight a pathogenic function for haem in triggering inflammatory responses through the activation of the nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome. Among the inflammasome multiprotein complexes, the NLRP3 inflammasome has been the most widely characterized as a trigger of inflammatory caspases and the maturation of interleukin-18 and -1β. In the present review, we discuss the latest evidence on the importance of inflammasome-mediated inflammation in pigment nephropathy. Finally, we highlight the potential role of inflammasome inhibitors in the prophylaxis and treatment of pigment nephropathy.
Highlights
Haem complexes consist of an Fe atom which is coordinated within the centre of a heterocyclic ring known as a protoporphyrin [1]
ureteral obstruction (UUO) mice treated with allopurinol exhibit less nucleotide-binding domain-like receptor protein 3 (NLRP3) and IL-1β expression within the UUO kidney compared to untreated UUO controls [53]
The release of haem by myoglobin and haemoglobin catabolism is pivotal in the pathogenesis of Pigment nephropathy (PN)
Summary
Haem complexes consist of an Fe atom which is coordinated within the centre of a heterocyclic ring known as a protoporphyrin [1]. Pigment nephropathy (PN) is an acute decline in kidney function following the breakdown and deposition of endogenous haem pigment-containing proteins (myoglobin, haemoglobin) within renal tissue [7]. Examples of HAMPs which activate the inflammasome are perturbed membrane potential through K+ efflux and Ca2+ influx [30], extracellular adenosine triphosphate (ATP) [31,32,33], and mitochondrial damage through reactive oxygen species (ROS) [34], altered mitochondrial membrane potential (∆Ψm) [35] and oxidised mitochondrial DNA (mtDNA) [36] While their activation triggers may be diverse, the signalling pathways of inflammasome activation can be categorized into either canonical or non-canonical activation
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