Caspase-11 Mediates Pyroptosis of Tubular Epithelial Cells and Septic Acute Kidney Injury

Ye, Zhiming; Zhang, Li; Li, Ruizhao; Dong, Wei; Liu, Shuangxin; Li, Zhilian; Liang, Huaban; Wang, Lifen; Shi, Wei; Malik, Asrar B.; Cheng, Kwong Tai; Liang, Xinling

doi:10.1159/000499685

Cited by 61 publications

(52 citation statements)

References 38 publications

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“…Pyroptosis is a form of inflammatory programed cell death pathway activated by human and mouse caspase1 and release of proinflammatory cytokines, including interleukin- (IL-) 1 β [ 39 ]. Pyroptotic cell death has been confirmed in LPS-induced AKI [ 15 ]. Our results show that mitochondria fission precedes caspase1 and IL-1 β activation involved pyroptosis occur in LPS-induced AKI.…”

Section: Discussionmentioning

confidence: 99%

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[Retracted] HO‐1/PINK1 Regulated Mitochondrial Fusion/Fission to Inhibit Pyroptosis and Attenuate Septic Acute Kidney Injury

Zhang

Sun

et al. 2020

BioMed Research International

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Background. Endotoxin-associated acute kidney injury (AKI), a disease characterized by marked oxidative stress and inflammation disease, is a major cause of mortality in critically ill patients. Mitochondrial fission and pyroptosis often occur in AKI. However, the underlying biological pathways involved in endotoxin AKI remain poorly understood, especially those related to mitochondrial dynamics equilibrium disregulation and pyroptosis. Previous studies suggest that heme oxygenase- (HO-) 1 confers cytoprotection against AKI during endotoxic shock, and PTEN-induced putative kinase 1 (PINK1) takes part in mitochondrial dysfunction. Thus, in this study, we examine the roles of HO-1/PINK1 in maintaining the dynamic process of mitochondrial fusion/fission to inhibit pyroptosis and mitigate acute kidney injury in rats exposed to endotoxin. Methods. An endotoxin-associated AKI model induced by lipopolysaccharide (LPS) was used in our study. Wild-type (WT) rats and PINK1 knockout (PINK1KO) rats, respectively, were divided into four groups: the control, LPS, Znpp+LPS, and Hemin+LPS groups. Rats were sacrificed 6 h after intraperitoneal injecting LPS to assess renal function, oxidative stress, and inflammation by plasma. Mitochondrial dynamics, morphology, and pyroptosis were evaluated by histological examinations. Results. In the rats with LPS-induced endotoxemia, the expression of HO-1 and PINK1 were upregulated at both mRNA and protein levels. These rats also exhibited inflammatory response, oxidative stress, mitochondrial fission, pyroptosis, and decreased renal function. After upregulating HO-1 in normal rats, pyroptosis was inhibited; mitochondrial fission and inflammatory response to oxidative stress were decreased; and the renal function was improved. The effects were reversed by adding Znpp (a type of HO-1 inhibitor). Finally, after PINK1 knockout, there is no statistical difference in the LPS-treated group and Hemin or Znpp pretreated group. Conclusions. HO-1 inhibits inflammation response and oxidative stress and regulates mitochondria fusion/fission to inhibit pyroptosis, which can alleviate endotoxin-induced AKI by PINK1.

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Section: Discussionmentioning

confidence: 99%

“…Once activated, caspase1 cleaves pro-IL-1 β into their mature forms, to induce pyroptosis [ 14 ]. Pyroptosis is involved in the death of renal tubular epithelial cells after exposure to microbial infection [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

[Retracted] HO‐1/PINK1 Regulated Mitochondrial Fusion/Fission to Inhibit Pyroptosis and Attenuate Septic Acute Kidney Injury

Zhang

Sun

et al. 2020

BioMed Research International

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“…In addition, the injection of IOP into mouse also increased the percentage of caspase-1 (+) PI (+) cells, IL-1β and IL-18 levels, LDH release activity, and the relative expression of NLRP3, ASC, caspase-1, GSDMD, and IL-1β. A previous study reported that caspase-11-mediated pyroptosis is closely related with Lipopolysaccharides (LPS)-induced septic AKI [36][37]. It is also reported that kidney epithelial pyroptosis played requisite roles in CI-AKI [38].…”

Section: Discussionmentioning

confidence: 98%

Acetylbritannilactone attenuates contrast-induced acute kidney injury through its anti-pyroptosis effects

Chen

Yang

et al. 2020

Bioscience Reports

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Contrast-induced acute kidney injury (CI-AKI) is a severe complication caused by intravascular applied radial contrast media (CM). Pyroptosis is a lytic type of cell death inherently associated with inflammation response and the secretion of pro-inflammatory cytokines following caspase-1 activation. The aim of the present study was to investigate the protective effects of acetylbritannilactone (ABL) on iopromide (IOP)-induced acute renal failure and reveal the underlying mechanism. In vivo and in vitro, IOP treatment caused renal damage and elevated the caspase-1 (+) propidium iodide (PI) (+) cell count, interleukin (IL)-1β and IL-18 levels, lactate dehydrogenase (LDH) release, and the relative expression of nucleotide-binding domain, leucine-rich repeat containing protein 3 (NLRP3), apoptosis-associated speck-like protein (ASC), and gasdermin D (GSDMD), suggesting that IOP induces AKI via the activation of pyroptosis. Furthermore, the pretreatment of ABL partly mitigated the CI-AKI, development of pyroptosis, and subsequent kidney inflammation. These data revealed that ABL partially prevents renal dysfunction and reduces pyroptosis in CI-AKI, which may provide a therapeutic target for the treatment of CM-induced AKI.

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“…To the best of our knowledge, this is the first study to report PD-induced NLRP3 inflammasome inactivation as a molecular mechanism of mitophagy in SI-AKI. Increasing studies have reported that inflammasome formation-induced activation of pyroptosis plays an important role in inflammatory diseases, including SI-AKI [39][40][41]. In the future, the effects of PD and sirtuins on pyroptosis should be explored further to identify more treatment targets for SI-AKI.…”

Section: Discussionmentioning

confidence: 99%

Role of Parkin-mediated mitophagy in the protective effect of polydatin in sepsis-induced acute kidney injury

Gao

Dai

et al. 2020

J Transl Med

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Background: We have reported that polydatin (PD) alleviates mitochondrial dysfunction in rat models of sepsisinduced acute kidney injury (SI-AKI), but the mechanism is not well understood. Here, we investigated the role of Parkin-mediated mitophagy in the protective effects of PD in SI-AKI in mice. Methods: Sepsis was induced in the mice by caecal ligation and puncture. Mitophagy was determined by mitochondrial mass. NLRP3 inflammasome activation was determined by NLRP3, ASC and caspase-1. Mitophagy was blocked by treatment with mitochondrial division inhibitor-1 and Parkin knockout. Key results: PD treatment increased the sepsis-induced loss of mitochondrial mass, indicating the upregulation of mitophagy. Furthermore, PD treatment mediated Parkin translocation from the cytoplasm to the mitochondria. This suggests that Parkin-mediated mitophagy is an underlying mechanism. This was confirmed by the suppression of PD-induced mitophagy in Parkin−/− mice and in mice that were treated with a mitophagy inhibitor. PD-induced Parkin translocation and mitophagy were blocked by inhibiting SIRT1; thus, activation of SIRT1 might be an important molecular mechanism that is triggered by PD. Additionally, PD treatment protected against sepsis-induced kidney injury. These effects were blocked by inhibition of Parkin-dependent mitophagy. Furthermore, PD also protected against mitochondrial dysfunction and mitochondria-dependent apoptosis, and the effect was blocked when Parkindependent mitophagy was inhibited. Finally, PD suppressed NLRP3 inflammasome activation that was also dependent on Parkin-mediated mitophagy. Conclusions: These findings indicate that Parkin-mediated mitophagy is important for the protective effect of PD in SI-AKI, and the underlying mechanisms include the inhibition of mitochondrial dysfunction and NLRP3 inflammasome activation.

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Caspase-11 Mediates Pyroptosis of Tubular Epithelial Cells and Septic Acute Kidney Injury

Cited by 61 publications

References 38 publications

[Retracted] HO‐1/PINK1 Regulated Mitochondrial Fusion/Fission to Inhibit Pyroptosis and Attenuate Septic Acute Kidney Injury

[Retracted] HO‐1/PINK1 Regulated Mitochondrial Fusion/Fission to Inhibit Pyroptosis and Attenuate Septic Acute Kidney Injury

Acetylbritannilactone attenuates contrast-induced acute kidney injury through its anti-pyroptosis effects

Role of Parkin-mediated mitophagy in the protective effect of polydatin in sepsis-induced acute kidney injury

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