Complement C3 mediates podocyte injury through TLR4/NFΚB-P65 signaling during ischemia–reperfusion acute kidney injury and post-injury fibrosis

Chen, Yi; Lin, Liyu; Rao, Siyi; Tao, Xuan; Cui, Jiong; Wan, Jianxin

doi:10.1186/s40001-023-01054-1

Cited by 2 publications

(2 citation statements)

References 44 publications

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“…In this study, in addition to reducing the expression of GFAP, SSD could also reduce PP‐induced C3 expression and significantly increase the levels of Ptx3 and S100a10. C3, the central molecule in the complement signaling pathway, is considered to be an important pro‐inflammatory molecule (Chen et al., 2023). Chen et al.…”

Section: Discussionmentioning

confidence: 99%

Saikosaponin D mitigate pilocarpine‐induced astrocyte injury by regulating the NLRP3/caspase‐1 signaling pathway

Liu,

Shen,

Zhu

et al. 2024

Chem Biol Drug Des

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Studies have shown that saikosaponin D (SSD) has favorable neurotherapeutic effects. Therefore, the objective of this study was to explore the efficacy and possible molecular mechanisms of SSD on pilocarpine (PP)‐induced astrocyte injury. Primary astrocytes were isolated from juvenile rats and identified using immunofluorescence. The cells were treated with PP and/or SSD for 6 h and 12 h, respectively, followed by measurement of their viability through 3‐(4,5‐dimethylthiazol)‐2,5‐diphenyl‐tetrazolium bromide (MTT) assay. Next, quantitative real‐time polymerase chain reaction (qRT‐PCR) was used to measure the expression levels of Glial fibrillary acidic protein (GFAP), C3, S100 calcium binding protein A10 (S100a10), pentraxin 3 (Ptx3), toll‐like receptor 4 (TLR4), and RAG in astrocytes after different treatments. Enzyme‐linked immunosorbent assay and biochemical tests were utilized to evaluate the level of inflammatory factors [interleukin (IL)‐1β, IL‐6, and tumor necrosis factor alpha (TNF‐α)] secreted by cells and the content of oxidative stress‐related factors (malondialdehyde [MDA] and glutathione [GSH]) or enzyme activity (catalase [CAT] and glutathione peroxidase [GPX]) in cells. The JC‐1 mitochondrial membrane potential (MMP) fluorescence probe was used to measure the MMP in astrocytes. Additionally, western blot was applied to test the expression of proteins related to the nod‐like receptor protein 3 (NLRP3)/caspase‐1 signaling pathway. PP treatment (1 mM) induced cell injury by significantly reducing the viability of astrocytes and expression of cellular markers. SSD treatment (4 μM) had no toxicity to astrocytes. Besides, SSD (4 μM) treatment could significantly up‐regulate the cell viability and marker expression of PP‐induced astrocytes. Furthermore, SSD could be employed to inhibit inflammation (reduce IL‐1β, IL‐6, and TNF‐α levels) and oxidative stress (decrease MDA level, elevate GSH level, the activity of CAT and GPX), and ameliorate mitochondrial dysfunction (upregulate JC‐1 ratio) in PP‐induced astrocytes. Moreover, further mechanism exploration revealed that SSD treatment significantly reduced the activity of the NLRP3/caspase‐1 signaling pathway activated by PP induction. SSD increased cell viability, inhibited inflammation and oxidative stress response, and ameliorated mitochondrial dysfunction in PP‐induced astrocyte injury model, thus playing a neuroprotective role. The mechanism of SSD may be related to the inhibition of the NLRP3/caspase‐1 inflammasome.

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Section: Discussionmentioning

confidence: 99%

Saikosaponin D mitigate pilocarpine‐induced astrocyte injury by regulating the NLRP3/caspase‐1 signaling pathway

Liu,

Shen,

Zhu

et al. 2024

Chem Biol Drug Des

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“…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%

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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Complement C3 mediates podocyte injury through TLR4/NFΚB-P65 signaling during ischemia–reperfusion acute kidney injury and post-injury fibrosis

Cited by 2 publications

References 44 publications

Saikosaponin D mitigate pilocarpine‐induced astrocyte injury by regulating the NLRP3/caspase‐1 signaling pathway

Saikosaponin D mitigate pilocarpine‐induced astrocyte injury by regulating the NLRP3/caspase‐1 signaling pathway

Complement activation in wasp venom-induced acute kidney injury

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