An Inhibitor of DRP1 (Mdivi-1) Alleviates LPS-Induced Septic AKI by Inhibiting NLRP3 Inflammasome Activation

Liu, Ruijin; Wang, Si-Cong; Li, Ming; Ma, Xuexiao; Jia, Xiaonan; Bu, Yue; Sun, Lei; Yu, Kaijiang

doi:10.1155/2020/2398420

Cited by 46 publications

(43 citation statements)

References 35 publications

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“…In rhabdomyolysis (RM)-induced AKI, Mdivi-1 treatment ameliorates renal function by maintaining the mitochondrial function and reducing the apoptosis of tubular cells [ 100 ]. In sepsis-induced AKI, Mdivi-1 treatment had renoprotective effect due to protection of mitochondrial function characterized by increasing ATP production and decreasing mitochondrial fragmentation, and the reduction of NOD-like receptor pyrin domain-3 (NLRP3) inflammasome-mediated pyroptosis of renal tubular epithelial cells [ 134 ]. Mdivi-1 also has been tested in CKD models; however, Mdivi-1 treatment seems to exhibit divergent functions in different studies.…”

Section: Mitochondrial Targeting For Aki and Ckd Therapymentioning

confidence: 99%

The Role of Mitochondria in Acute Kidney Injury and Chronic Kidney Disease and Its Therapeutic Potential

Zhang

Agborbesong

2021

IJMS

107

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Mitochondria are heterogeneous and highly dynamic organelles, playing critical roles in adenosine triphosphate (ATP) synthesis, metabolic modulation, reactive oxygen species (ROS) generation, and cell differentiation and death. Mitochondrial dysfunction has been recognized as a contributor in many diseases. The kidney is an organ enriched in mitochondria and with high energy demand in the human body. Recent studies have been focusing on how mitochondrial dysfunction contributes to the pathogenesis of different forms of kidney diseases, including acute kidney injury (AKI) and chronic kidney disease (CKD). AKI has been linked to an increased risk of developing CKD. AKI and CKD have a broad clinical syndrome and a substantial impact on morbidity and mortality, encompassing various etiologies and representing important challenges for global public health. Renal mitochondrial disorders are a common feature of diverse forms of AKI and CKD, which result from defects in mitochondrial structure, dynamics, and biogenesis as well as crosstalk of mitochondria with other organelles. Persistent dysregulation of mitochondrial homeostasis in AKI and CKD affects diverse cellular pathways, leading to an increase in renal microvascular loss, oxidative stress, apoptosis, and eventually renal failure. It is important to understand the cellular and molecular events that govern mitochondria functions and pathophysiology in AKI and CKD, which should facilitate the development of novel therapeutic strategies. This review provides an overview of the molecular insights of the mitochondria and the specific pathogenic mechanisms of mitochondrial dysfunction in the progression of AKI, CKD, and AKI to CKD transition. We also discuss the possible beneficial effects of mitochondrial-targeted therapeutic agents for the treatment of mitochondrial dysfunction-mediated AKI and CKD, which may translate into therapeutic options to ameliorate renal injury and delay the progression of these kidney diseases.

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Section: Mitochondrial Targeting For Aki and Ckd Therapymentioning

confidence: 99%

The Role of Mitochondria in Acute Kidney Injury and Chronic Kidney Disease and Its Therapeutic Potential

Zhang

Agborbesong

2021

IJMS

107

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“…Pyroptosis is a new type of programmed cell death mediated by the gasdermin D protein and characterized by the release of inflammatory mediators (5). Recently, pyroptosis has become a research hotspot in cancer initiation and progression.…”

Section: Introductionmentioning

confidence: 99%

A Pyroptosis-Related Gene Signature for Predicting Survival in Glioblastoma

Zhang

et al. 2021

Front. Oncol.

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BackgroundIn this study, a prognostic model based on pyroptosis-related genes was established to predict overall survival (OS) in patients with glioblastoma (GBM).MethodsThe gene expression data and clinical information of GBM patients were obtained from The Cancer Genome Atlas (TCGA), and bioinformatics analysis of differentially expressed genes was performed. LASSO Cox regression model was used to construct a three-pyroptosis-related gene signature, and validation was performed using an experimental cohort.ResultsA total of three pyroptosis-related genes (CASP4, CASP9, and NOD2) were used to construct a survival prognostic model, and experimental validation was performed using an experimental cohort. Receiver operating characteristic (ROC) analysis was performed, and the area under the ROC curves (AUC) was 0.921, 0.840, and 0.905 at 1, 3, and 5 years, respectively. Functional analysis revealed that T-cell activation, regulation of T-cell activation, leukocyte cell-cell adhesion, and positive regulation of cell adhesion among other immune-related functions were enriched, and immune-related processes were different between the two risk groups.ConclusionIn this study, a novel prognostic model based on three pyroptosis-related genes is constructed and used to predict the prognosis of GBM patients. The model can accurately and conveniently predict the 1-, 3-, and 5-year OS of GBM patients.

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“…In a model of cell sepsis‐induced acute kidney injury (S‐AKI), Mdivi‐1 treatment inhibited mitochondrial fragmentation which prevented the release of mitochondrial contents and decreased NLRP3 activation in renal tubular epithelial cells. Mdivi‐1 treatment also alleviated kidney damage in LPS‐induced S‐AKI mice (Liu et al , 2020 ). The NLRP3 inflammasome is now a target of significant interest in the treatment of inflammatory diseases (Coll et al , 2015 ), and NLRP3 inflammasome activation serves as a critical step in the inflammatory response against pathogens.…”

Section: Sarsmentioning

confidence: 99%

Alterations in mitochondrial morphology as a key driver of immunity and host defence

2021

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Mitochondria are dynamic organelles whose architecture changes depending on the cell’s energy requirements and other signalling events. These structural changes are collectively known as mitochondrial dynamics. Mitochondrial dynamics are crucial for cellular functions such as differentiation, energy production and cell death. Importantly, it has become clear in recent years that mitochondrial dynamics are a critical control point for immune cell function. Mitochondrial remodelling allows quiescent immune cells to rapidly change their metabolism and become activated, producing mediators, such as cytokines, chemokines and even metabolites to execute an effective immune response. The importance of mitochondrial dynamics in immunity is evident, as numerous pathogens have evolved mechanisms to manipulate host cell mitochondrial remodelling in order to promote their own survival. In this review, we comprehensively address the roles of mitochondrial dynamics in immune cell function, along with modulation of host cell mitochondrial morphology during viral and bacterial infections to facilitate either pathogen survival or host immunity. We also speculate on what the future may hold in terms of therapies targeting mitochondrial morphology for bacterial and viral control.

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An Inhibitor of DRP1 (Mdivi-1) Alleviates LPS-Induced Septic AKI by Inhibiting NLRP3 Inflammasome Activation

Cited by 46 publications

References 35 publications

The Role of Mitochondria in Acute Kidney Injury and Chronic Kidney Disease and Its Therapeutic Potential

The Role of Mitochondria in Acute Kidney Injury and Chronic Kidney Disease and Its Therapeutic Potential

A Pyroptosis-Related Gene Signature for Predicting Survival in Glioblastoma

Alterations in mitochondrial morphology as a key driver of immunity and host defence

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