How Kidney Cell Death Induces Renal Necroinflammation
Section snippets
Evolutional Origins of Inflammation
Any multicellular organism has to maintain the integrity of its tissues. Because multicellular organisms frequently face traumatic injuries, suitable danger response programs need to immediately control the potential fatal threats of fluid (blood) loss, pathogen entry, and tissue instability.18 Plants and animals control these three fundamental dangers by clotting, inflammation, and wound healing, respectively,19 whereas wound healing implies re-epithelialization and scarring.20 Evolution
Renal Cell Necrosis as a Source of Intracellular DAMPs
Genetically controlled forms of necrosis are referred to as regulated necrosis (RN), that is, necroptosis is a receptor-interacting serine/threonine-protein kinase (RIPK)3- and MLKL-mediated form of necrosis.98 Renal cell necroptosis contributes to ATN in several models of kidney injuries.99, 100, 101, 102 Necroptosis involves the release of the alarmin IL-33, which induces inflammation.98, 103 In addition, cyclophilin D–mediated mitochondrial permeability transition-related RN also was
Kidney Diseases with Renal Cell Necrosis
Necrotic lesions inside the kidney usually are driven by a primary vascular necrosis (eg, in crescentic glomerulonephritis or thrombotic microangiopathies). In addition, ischemic tubular necrosis has an important component of peritubular vascular necrosis. We discuss the evidence for necrotic cell death driving inflammation in these disease entities.
Summary
Renal cell loss is rarely a consequence of apoptosis but rather of regulated necrosis, or simply flushing of detached living cells. During AKI, regulated necrosis seems most prevalent, for example, during necrotizing glomerulonephritis, acute tubular necrosis, or thrombotic microangiopathies. Immune cell necrosis (ie, NETosis or pyroptosis), is a likely component of these disorders. Necrosis involves rupture of the plasma membrane, which implies the release of DAMPs and alarmins that ligate
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2023, Recent Developments in Anti-Inflammatory TherapyHDAC5 RNA interference ameliorates acute renal injury by upregulating KLF2 and inhibiting NALP3 expression in a mouse model of oxalate nephropathy
2022, International ImmunopharmacologyCitation Excerpt :These interstitial CaOx crystals are internalized by tubular epithelial cells through phagocytosis which results in cellular necrosis via RIPK3/MLKL pathway. Necrosis induced by CaOx causes the release of Danger associated molecular patterns (DAMPs), which activates canonical NALP3/ASC/ caspase-1 inflammasome in Macrophages, neutrophils, and Dendritic cells (DC) resulting in secretion of cytokines (IL-1β, TNF-α, IL-8, IL-18), initiation of cellular injury, generation of reactive oxygen species (ROS), necroinflammation and subsequently end stage renal failure [40–42]. Here we have investigated the functional role of HDAC5 in the regulation of KLF2 and NLAP3 in the context of acute crystal-induced renal injury.
6,7-Dihydroxycoumarin ameliorates crystal-induced necroptosis during crystal nephropathies by inhibiting MLKL phosphorylation
2021, Life SciencesCitation Excerpt :Consistently, here we found that 6,7-DHC pretreatment protected cells from crystal-induced mitochondrial dysfunction and subsequent necroptosis emphasizing the significant interference of these pathways during crystal cytotoxicity. Cellular necrosis and inflammation form a positive feedback loop, termed necroinflammation that contributes to various kidney diseases [51,52]. Interestingly, recent studies demonstrated the involvement of MLKL-mediated necroinflammation not only in AKI but also in its progression to CKD [16,53].
Desmoid-type fibromatosis of the lower extremity: A unique case of complete lesion resolution following core needle biopsy
2021, Clinical ImagingCitation Excerpt :Other case reports of post-biopsy tumor resolution include merkel cell carcinomas, renal malignancies, squamous cell carcinomas (skin and lung), primary breast lymphoma, and pulmonary adenocarcinoma [40–45,49,50]. The exact mechanism of biopsy induced regression remains unclear with immunologic and tumor necrosis among many mechanisms suggested [45,51–53]. In summary, DF exhibits a range of variable behavior and a flexible clinical approach is needed to maximize clinical outcomes.
Financial support: Supported by the Deutsche Forschungsgemeinschaft (MU 3906/1-1, AN372/11-2, 14-3, 16-1, 20-1, and 23-1 to S.R.M. and H.-J.A.).
Conflicts of interest statement: none.