Caspase-1 Inhibitor Reduces Pyroptosis Induced by Brain Death in Kidney

Liu, Weifeng; Yang, Dawei; Shi, Jihua; Zhang, Jiakai; Wang, Zhi‐Hui; Hu, Bowen; Shi, Xiaohong; Cao, Shengli; Guo, Wenzhi; Zhang, Shuijun

doi:10.3389/fsurg.2021.760989

Cited by 8 publications

(5 citation statements)

References 37 publications

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“…Pyroptosis is a type of programmed cell necrosis mediated by GSDMD [ 13 ]. Caspase-1, which mediates classical pathway of pyroptosis, belongs to the caspase subfamily and play key roles in immune response-related signaling [ 14 ]. GSDMD, which is identified as a substrate of caspase-1, is primarily expressed in immune cells and shows unique structural characteristics of a perforating protein [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

Role of hypoxia-mediated pyroptosis in the development of extending knee joint contracture in rats

Zhang,

Huo,

et al. 2024

Eur J Med Res

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Joint contracture is one of the common diseases clinically, and joint capsule fibrosis is considered to be one of the most important pathological changes of joint contracture. However, the underlying mechanism of joint capsule fibrosis is still controversial. The present study aims to establish an animal model of knee extending joint contracture in rats, and to investigate the role of hypoxia-mediated pyroptosis in the progression of joint contracture using this animal model. 36 male SD rats were selected, 6 of which were not immobilized and were used as control group, while 30 rats were divided into I-1 group (immobilized for 1 week following 7 weeks of free movement), I-2 group (immobilized for 2 weeks following 6 weeks of free movement), I-4 group (immobilized for 4 weeks following 4 weeks of free movement), I-6 group (immobilized for 6 weeks following 2 weeks of free movement) and I-8 group (immobilized for 8 weeks) according to different immobilizing time. The progression of joint contracture was assessed by the measurement of knee joint range of motion, collagen deposition in joint capsule was examined with Masson staining, protein expression levels of HIF-1α, NLRP3, Caspase-1, GSDMD-N, TGF-β1, α-SMA and p-Smad3 in joint capsule were assessed using western blotting, and the morphological changes of fibroblasts were observed by transmission electron microscopy. The degree of total and arthrogenic contracture progressed from the first week and lasted until the first eight weeks after immobilization. The degree of total and arthrogenic contracture progressed rapidly in the first four weeks after immobilization and then progressed slowly. Masson staining indicated that collagen deposition in joint capsule gradually increased in the first 8 weeks following immobilization. Western blotting analysis showed that the protein levels of HIF-1α continued to increase during the first 8 weeks of immobilization, and the protein levels of pyroptosis-related proteins NLRP3, Caspase-1, GSDMD-N continued to increase in the first 4 weeks after immobilization and then decreased. The protein levels of fibrosis-related proteins TGF-β1, p-Smad3 and α-SMA continued to increase in the first 8 weeks after immobilization. Transmission electron microscopy showed that 4 weeks of immobilization induced cell membrane rupture and cell contents overflow, which further indicated the activation of pyroptosis. Knee extending joint contracture animal model can be established by external immobilization orthosis in rats, and the activation of hypoxia-mediated pyroptosis may play a stimulating role in the process of joint capsule fibrosis and joint contracture.

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Section: Introductionmentioning

confidence: 99%

Role of hypoxia-mediated pyroptosis in the development of extending knee joint contracture in rats

Zhang,

Huo,

et al. 2024

Eur J Med Res

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“…Moreover, Z-YVAD-FMK, as a caspase-1 inhibitor, inhibited duck renal TEC pyroptosis, which relieved Cd-induced nephrotoxicity [ 146 ]. Z-YVAD-FMK efficaciously also reduced pyroptosis effects on BD-induced kidney injury [ 147 ]. In 2022, recent results showed the selective caspase-1 inhibitor VX-765 downregulated pyroptosis-associated protein in glucose-induced TCEs and diabetic mice [ 148 ].…”

Section: Therapeutic Treatment Of Blocking Pyroptosis In Kidney Diseasesmentioning

confidence: 99%

The Role of Pyroptosis in the Pathogenesis of Kidney Diseases

Zhou¹,

Li²

2023

Kidney Dis

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Background: Recently, in addition to apoptosis and necrosis, several other forms of cell death have been discovered, such as necroptosis, autophagy, pyroptosis, and ferroptosis. These cell death modalities play diverse roles in kidney diseases. Pyroptosis is a newly described type of pro-inflammatory programmed necrosis. Further exploring pyroptosis is helpful to slow the progression of kidney diseases and reduce their complications. Summary: Pyroptosis is mainly mediated by the cleavage of gasdermin D (GSDMD) along with downstream inflammasome activation. Activated-caspase-1 induces the release of cytokines by cleaving GSDMD. Inflammation is a major pathogenic mechanism for kidney diseases. Increasing evidence corroborated that pyroptosis was closely related to the progression of renal diseases, including acute kidney injury, renal fibrosis, diabetic nephropathy, kidney cancer. In this paper, we reviewed the role and the therapeutic treatment of pyroptosis in renal diseases. Key Messages: The better understanding of the progress and new intervention approaches of pyroptosis in kidney diseases, which may pave the way for new therapeutic opportunities in clinical practice.

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“…Moreover, it differs from other pore-forming RCDs, such as necroptosis, by involving the gasdermin (GSDM) family of proteins as the membrane poreforming agent [24]. It manifests by activation of one or more caspases, primarily caspase-1 in humans and mice, human caspase-4/5 in humans and caspase-11 in mice [61,62] and thus can broadly be classified into canonical caspase-1 dependent and non-canonical caspase-1 independent pyroptosis. Both the types, however, remain morphologically similar.…”

Section: Pyroptosismentioning

confidence: 99%

Revisiting Regulated Cell Death Responses in Viral Infections

Rex

Prasad

Kandasamy

2022

IJMS

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The fate of a viral infection in the host begins with various types of cellular responses, such as abortive, productive, latent, and destructive infections. Apoptosis, necroptosis, and pyroptosis are the three major types of regulated cell death mechanisms that play critical roles in viral infection response. Cell shrinkage, nuclear condensation, bleb formation, and retained membrane integrity are all signs of osmotic imbalance-driven cytoplasmic swelling and early membrane damage in necroptosis and pyroptosis. Caspase-driven apoptotic cell demise is considered in many circumstances as an anti-inflammatory, and some pathogens hijack the cell death signaling routes to initiate a targeted attack against the host. In this review, the selected mechanisms by which viruses interfere with cell death were discussed in-depth and were illustrated by compiling the general principles and cellular signaling mechanisms of virus–host-specific molecule interactions.

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Caspase-1 Inhibitor Reduces Pyroptosis Induced by Brain Death in Kidney

Cited by 8 publications

References 37 publications

Role of hypoxia-mediated pyroptosis in the development of extending knee joint contracture in rats

Role of hypoxia-mediated pyroptosis in the development of extending knee joint contracture in rats

The Role of Pyroptosis in the Pathogenesis of Kidney Diseases

Revisiting Regulated Cell Death Responses in Viral Infections

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