E-prostanoid 3 receptor deficiency on myeloid cells protects against ischemic acute kidney injury via breaking the auto-amplification loop of necroinflammation

Leng, Jing; Zhao, Wen; Guo, Jinwei; Yu, Gang; Zhu, Guoqiang; Ge, Jiahui; He, Dong; Xu, Yineng; Chen, Xijian; Zhou, Yingbi; Liu, Bin

doi:10.1016/j.kint.2022.08.019

Cited by 9 publications

(10 citation statements)

References 63 publications

(123 reference statements)

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“…Recent reports have suggested that myeloid immune cells may be critical for necroinflammation-mediated next wave of cell death, especially macrophages, DCs, and neutrophils [ 34 , 35 ]. Therefore, we assessed the myeloid immune cell infiltration difference of the two risk groups using ssGSEA, which revealed a higher abundance of immature or plasmacytoid DCs, eosinophils, and macrophages in the high-risk group (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…However, recently, there has been further understanding of such cell deaths during AKI, as detailed in the previous sections. Therefore, while blocking ferroptosis resulted in a greater benefit for renal hypofunction within the initial 24 h after reperfusion, the vehicle targeting the necroinflammatory-associated necroptosis-associated pathway did cut off the vicious loop to prevent the ensuing cell loss [ 32 – 34 , 66 ]. Consequently, early mitigation of cell loss is crucial to achieving PPPM in post-KTx patients.…”

Section: Discussionmentioning

confidence: 99%

“…In 2012, Linkermann et al identified that TNF-α-mediated Rip1-dependent post-IRI renal tubular epithelial cell death could be ameliorated by necrostatin-1 (Nec-1); it could also attenuate organ injury and failure, providing initial evidence for necroptosis-related tubular cell loss [ 65 ]. TNF-α, commonly elevated after IRI, is considered to be one of the key molecules triggering necroptosis, and the in vitro application of Nec-1 has been found to mitigate the death of murine tubular epithelial cells [ 34 , 65 , 70 ]. Recent reports have demonstrated that the upregulated TWEAK/Fn14 pathway during AKI promotes the release of MCP-1 and IL-6 from bone marrow-derived immune cells and proximal tubular cells via the RIPK3-evoked activation of NF-κB; these inflammatory factors subsequently mediate a necroptosis-dependent second wave of tubular cell death [ 35 ].…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, RIPK1 is also implicated in the mediation of TRIF-dependent NF-κB activation via TLR3/4 [ 71 ]. In addition, Leng et al reported that EP3 signaling can also mediate necroinflammatory responses to promote necroptosis, while EP3-deficiency ameliorates IRI-induced AKI by breaking the cycle from necroinflammation to RN [ 34 ]. Moreover, IL-6 is capable of activating the JAK-STAT signaling pathway [ 72 , 73 ], which could downregulate the caspases, including caspase-8 (the switch between necroptosis and apoptosis) [ 74 ].…”

Section: Discussionmentioning

confidence: 99%

“…On the other hand, ferroptosis, necroptosis, and apoptosis are substitutable; inhibition in one pathway causes cells to be sensitive to death through another pathway [ 33 , 34 , 36 ]. While early blockade of the necroptosis-related pathway lacks a significant protective effect on renal function in the first 48 h, it is effective in preventing vicious cycling and improving the prognosis of renal function [ 33 , 34 ].

Fig.…”

Section: Introductionmentioning

confidence: 99%

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Identification of potential necroinflammation-associated necroptosis-related biomarkers for delayed graft function and renal allograft failure: a machine learning-based exploration in the framework of predictive, preventive, and personalized medicine

Qiu

et al. 2023

EPMA Journal

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Delayed graft function (DGF) is one of the key post-operative challenges for a subset of kidney transplantation (KTx) patients. Graft survival is significantly lower in recipients who have experienced DGF than in those who have not. Assessing the risk of chronic graft injury, predicting graft rejection, providing personalized treatment, and improving graft survival are major strategies for predictive, preventive, and personalized medicine (PPPM/3PM) to promote the development of transplant medicine. However, since PPPM aims to accurately identify disease by integrating multiple omics, current methods to predict DGF and graft survival can still be improved. Renal ischemia/reperfusion injury (IRI) is a pathological process experienced by all KTx recipients that can result in varying occurrences of DGF, chronic rejection, and allograft failure depending on its severity. During this process, a necroinflammation-mediated necroptosis-dependent secondary wave of cell death significantly contributes to post-IRI tubular cell loss. In this article, we obtained the expression matrices and corresponding clinical data from the GEO database. Subsequently, nine differentially expressed necroinflammation-associated necroptosis-related genes (NiNRGs) were identified by correlation and differential expression analysis. The subtyping of post-KTx IRI samples relied on consensus clustering; the grouping of prognostic risks and the construction of predictive models for DGF (the area under the receiver operating characteristic curve (AUC) of the internal validation set and the external validation set were 0.730 and 0.773, respectively) and expected graft survival after a biopsy (the internal validation set’s 1-year AUC: 0.770; 2-year AUC: 0.702; and 3-year AUC: 0.735) were based on the least absolute shrinkage and selection operator regression algorithms. The results of the immune infiltration analysis showed a higher infiltration abundance of myeloid immune cells, especially neutrophils, macrophages, and dendritic cells, in the cluster A subtype and prognostic high-risk groups. Therefore, in the framework of PPPM, this work provides a comprehensive exploration of the early expression landscape, related pathways, immune features, and prognostic impact of NiNRGs in post-KTx patients and assesses their capabilities as. predictors of post-KTx DGF and graft loss, targets of the vicious loop between regulated tubular cell necrosis and necroinflammation for targeted secondary and tertiary prevention, and references for personalized immunotherapy. Supplementary Information The online version contains supplementary material available at 10.1007/s13167-023-00320-w.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Fig.…”

Section: Introductionmentioning

confidence: 99%

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Identification of potential necroinflammation-associated necroptosis-related biomarkers for delayed graft function and renal allograft failure: a machine learning-based exploration in the framework of predictive, preventive, and personalized medicine

Qiu

et al. 2023

EPMA Journal

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Neutrophil‐Mediated Nanozyme Delivery System for Acute Kidney Injury Therapy

Yang,

Du,

Gan

et al. 2024

Adv Healthcare Materials

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Reactive oxygen species (ROS) scavenging of nanozymes toward acute kidney injury (AKI) is a current promising strategy, however, the glomerular filtration barrier (GFB) limits their application for treating kidney related diseases. Here, a neutrophil‐mediated delivery system able to hijack neutrophil to transport nanozyme‐loaded cRGD‐liposomes to inflamed kidney for AKI treatment by cRGD targeting integrin αvβ1 is reported. The neutrophil‐mediated nanozyme delivery system demonstrated great antioxidant and anti‐apoptosis ability in HK‐2 and NRK‐52E cell lines. Moreover, in ischemia‐reperfusion (I/R) induced AKI mice, a single dose of LM@cRGD‐LPs 12 h post‐ischemia significantly reduces renal function indicators, alleviates renal pathological changes, and inhibits apoptosis of renal tubular cells and the expression of renal tubular injured marker, thus remarkably reducing the damage of AKI. Mechanistically, the treatment of LM@cRGD‐LPs markedly inhibits the process of Nrf2 to the nucleus and reduces the expression of the downstream HO‐1, achieves a 99.51% increase in renal tissue Nrf2 levels, and an 86.31% decrease in HO‐1 levels after LM@cRGD‐LPs treatment. In short, the strategy of neutrophil‐mediated nanozyme delivery system hold great promise as a potential therapy for AKI or other inflammatory diseases.

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Emerging insights into the pathogenesis and therapeutic strategies for vascular endothelial injury-associated diseases: focus on mitochondrial dysfunction

Pang,

Dong,

Pang

et al. 2024

Angiogenesis

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As a vital component of blood vessels, endothelial cells play a key role in maintaining overall physiological function by residing between circulating blood and semi-solid tissue. Various stress stimuli can induce endothelial injury, leading to the onset of corresponding diseases in the body. In recent years, the importance of mitochondria in vascular endothelial injury has become increasingly apparent. Mitochondria, as the primary site of cellular aerobic respiration and the organelle for “energy information transfer,” can detect endothelial cell damage by integrating and receiving various external stress signals. The generation of reactive oxygen species (ROS) and mitochondrial dysfunction often determine the evolution of endothelial cell injury towards necrosis or apoptosis. Therefore, mitochondria are closely associated with endothelial cell function, helping to determine the progression of clinical diseases. This article comprehensively reviews the interconnection and pathogenesis of mitochondrial-induced vascular endothelial cell injury in cardiovascular diseases, renal diseases, pulmonary-related diseases, cerebrovascular diseases, and microvascular diseases associated with diabetes. Corresponding therapeutic approaches are also provided. Additionally, strategies for using clinical drugs to treat vascular endothelial injury-based diseases are discussed, aiming to offer new insights and treatment options for the clinical diagnosis of related vascular injuries.

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E-prostanoid 3 receptor deficiency on myeloid cells protects against ischemic acute kidney injury via breaking the auto-amplification loop of necroinflammation

Cited by 9 publications

References 63 publications

Identification of potential necroinflammation-associated necroptosis-related biomarkers for delayed graft function and renal allograft failure: a machine learning-based exploration in the framework of predictive, preventive, and personalized medicine

Identification of potential necroinflammation-associated necroptosis-related biomarkers for delayed graft function and renal allograft failure: a machine learning-based exploration in the framework of predictive, preventive, and personalized medicine

Neutrophil‐Mediated Nanozyme Delivery System for Acute Kidney Injury Therapy

Emerging insights into the pathogenesis and therapeutic strategies for vascular endothelial injury-associated diseases: focus on mitochondrial dysfunction

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