STING deficiency protects against wasp venom-induced acute kidney injury

Liu, Ying; Lü, Li; Yu, Fanglin; Gao, Zhao; Yuan, Hai; Hu, Fengqi

doi:10.1007/s00011-023-01749-5

Cited by 5 publications

(7 citation statements)

References 44 publications

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“…However, it remains unclear whether the STING signaling pathway is activated and plays a role in the development of wasp venom-induced AKI. More recently, STING knockout or pharmacological inhibition in vivo data, as well as STING knockdown in vitro data, revealed that STING-TBK1/IRF3 signaling pathway plays a central role in regulating the inflammatory response and inflammation mediators (IL-6, MCP-1, IFN-α, and IFN-β) in wasp venom-induced AKI [ 65 ]. Further studies are needed to explore the mechanism of STING activation in wasp venom-induced AKI.…”

Section: Aki Pathophysiology Induced By Wasp Venommentioning

confidence: 99%

Wasp venom-induced acute kidney injury: current progress and prospects

Yu,

Wang,

Yuan

et al. 2023

Renal Failure

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Wasp venom can trigger local and systemic reactions, with the kidneys being commonly affected, potentially causing acute kidney injury (AKI). Despite of the recent advances, our knowledge on the underlying mechanisms of toxicity and targeted therapies remain poor. AKI can result from direct nephrotoxic effects of the wasp venom or secondary rhabdomyolysis and intravascular hemolysis, which will release myoglobin and free hemoglobin. Inflammatory responses play a central role in these pathological mechanisms. Noteworthily, the successful establishment of a suitable experimental model can assist in basic research and clinical advancements related to wasp venom-induced AKI. The combination of therapeutic plasma exchange and continuous renal replacement therapy appears to be the preferred treatment for wasp venom-induced AKI. In addition, studies on cilastatin and varespladib for wasp venom-induced AKI treatment have shown their potential as therapeutic agents. This review summarizes the available evidence on the mechanisms and treatment of wasp venom-induced AKI, with a particular focus on the role of inflammatory responses and potential targets for therapeutic drugs, and, therefore, aiming to support the development of clinical treatment against wasp venom-induced AKI.

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Section: Aki Pathophysiology Induced By Wasp Venommentioning

confidence: 99%

Wasp venom-induced acute kidney injury: current progress and prospects

Yu,

Wang,

Yuan

et al. 2023

Renal Failure

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“…Immunofluorescence assays were performed on paraffin-embedded renal tissue sections, following the method described in our previous study [ 17 ]. The present study used the following antibodies: anti-C3 (1:500, ab200999, Abcam, Cambridge, UK), anti-C1q (1:500, ab182451, Abcam), anti-FB (1:500, 10170-1-AP, Proteintech, Wuhan, China), and anti-MBL (1:500, HM1038, Hycult Biotech, Uden, The Netherlands).…”

mentioning

confidence: 99%

“…Real-time quantitative PCR was performed using the QuantStudio 12K Flex Real-Time PCR System (Applied Biosystems, Foster City, CA, USA), and gene expression levels were quantified based on the 2-ΔΔCt method. The C5b-9 levels in kidneys were measured using an enzyme-linked immunosorbent assay (ELISA) kit (E-EL-M1129c, Elabscience, Wuhan, China) as previously described [ 17 ].…”

mentioning

confidence: 99%

“…Previous studies have provided evidence that local complement activation in the kidney can induce cell death and inflammation during AKI development [ 12 , 25 ]. Our previous studies have shown that cell death (apoptosis, necroptosis) and inflammation in the kidney are significant features of wasp venom-induced AKI [ 17 , 22 ]. Additionally, C5b-9 has been found to play a pathological role in the kidneys.…”

mentioning

confidence: 99%

“…C5b-9 may contribute to wasp venom-induced AKI by inducing kidney cell death and promoting inflammation. Our recent studies have highlighted the significant contribution of cell death and inflammation to the development of AKI induced by wasp venom [ 11 , 17 , 22 ]. These findings suggest an association between complement activation and cell death and inflammation in wasp venom-induced AKI.…”

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confidence: 99%

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Complement activation in wasp venom-induced acute kidney injury

Cheng,

Xu,

Gong

et al. 2024

Renal Failure

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Previous studies have highlighted the significant role of complement activation in kidney injuries induced by rhabdomyolysis, intravascular hemolysis, sepsis, and ischemia-reperfusion. Nevertheless, the specific role and mechanism of complement activation in acute kidney injury (AKI) caused by wasp venom remain unclear. The aim of this study was to elucidate the specific complement pathway activated and investigate complement activation in AKI induced by wasp venom. In this study, a complement-depleted mouse model was used to investigate the role of complement in wasp venom-induced AKI. Mice were randomly categorized into control, cobra venom factor (CVF), AKI, and CVF + AKI groups. Compared to the AKI group, the CVF + AKI group showed improved pathological changes in kidneys and reduced blood urea nitrogen (BUN) levels. The expression levels of renal complement 3 (C3), complement 5 (C5), complement 1q (C1q), factor B (FB), mannose-binding lectin (MBL), and C5b-9 in AKI group were upregulated compared with the control group. Conversely, the renal tissue expression levels of C3, C5, C1q, FB, MBL, and C5b-9 were decreased in the CVF + AKI group compared to those in the AKI group. Complement activation occurs through all three pathways in AKI induced by wasp venom. Furthermore, complement depletion by CVF attenuates wasp venom-induced nephrotoxicity, suggesting that complement activation plays a primary role in the pathogenesis of wasp venom-induced AKI.

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