4
views
0
recommends
+1 Recommend
2 collections
    0
    shares

      Call for Papers: Digital Platforms and Artificial Intelligence in Dementia

      Submit here by August 31, 2025

      About Dementia and Geriatric Cognitive Disorders: 2.2 Impact Factor I 4.7 CiteScore I 0.809 Scimago Journal & Country Rank (SJR)

      Call for Papers: Epidemiology of CKD and its Complications

      Submit here by August 31, 2024

      About Kidney and Blood Pressure Research: 2.3 Impact Factor I 4.8 CiteScore I 0.674 Scimago Journal & Country Rank (SJR)

      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      The Role of Pyroptosis in the Pathogenesis of Kidney Diseases

      review-article
      ,
      Kidney Diseases
      S. Karger AG
      Kidney diseases, Pyroptosis, Inflammation, Programmed cell death, Therapeutic drugs

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          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 proinflammatory 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, and 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 may pave the way for new therapeutic opportunities in clinical practice.

          Related collections

          Most cited references152

          • Record: found
          • Abstract: found
          • Article: not found

          Chemotherapy drugs induce pyroptosis through caspase-3 cleavage of a Gasdermin

          Pyroptosis is a form of cell death that is critical for immunity. It can be induced by the canonical caspase-1 inflammasomes or by activation of caspase-4, -5 and -11 by cytosolic lipopolysaccharide. The caspases cleave gasdermin D (GSDMD) in its middle linker to release autoinhibition on its gasdermin-N domain, which executes pyroptosis via its pore-forming activity. GSDMD belongs to a gasdermin family that shares the pore-forming domain. The functions and mechanisms of activation of other gasdermins are unknown. Here we show that GSDME, which was originally identified as DFNA5 (deafness, autosomal dominant 5), can switch caspase-3-mediated apoptosis induced by TNF or chemotherapy drugs to pyroptosis. GSDME was specifically cleaved by caspase-3 in its linker, generating a GSDME-N fragment that perforates membranes and thereby induces pyroptosis. After chemotherapy, cleavage of GSDME by caspase-3 induced pyroptosis in certain GSDME-expressing cancer cells. GSDME was silenced in most cancer cells but expressed in many normal tissues. Human primary cells exhibited GSDME-dependent pyroptosis upon activation of caspase-3 by chemotherapy drugs. Gsdme-/- (also known as Dfna5-/-) mice were protected from chemotherapy-induced tissue damage and weight loss. These findings suggest that caspase-3 activation can trigger necrosis by cleaving GSDME and offer new insights into cancer chemotherapy.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Pyroptosis: Gasdermin-Mediated Programmed Necrotic Cell Death.

            Pyroptosis was long regarded as caspase-1-mediated monocyte death in response to certain bacterial insults. Caspase-1 is activated upon various infectious and immunological challenges through different inflammasomes. The discovery of caspase-11/4/5 function in sensing intracellular lipopolysaccharide expands the spectrum of pyroptosis mediators and also reveals that pyroptosis is not cell type specific. Recent studies identified the pyroptosis executioner, gasdermin D (GSDMD), a substrate of both caspase-1 and caspase-11/4/5. GSDMD represents a large gasdermin family bearing a novel membrane pore-forming activity. Thus, pyroptosis is redefined as gasdermin-mediated programmed necrosis. Gasdermins are associated with various genetic diseases, but their cellular function and mechanism of activation (except for GSDMD) are unknown. The gasdermin family suggests a new area of research on pyroptosis function in immunity, disease, and beyond.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              The inflammasomes.

              Inflammasomes are molecular platforms activated upon cellular infection or stress that trigger the maturation of proinflammatory cytokines such as interleukin-1beta to engage innate immune defenses. Strong associations between dysregulated inflammasome activity and human heritable and acquired inflammatory diseases highlight the importance this pathway in tailoring immune responses. Here, we comprehensively review mechanisms directing normal inflammasome function and its dysregulation in disease. Agonists and activation mechanisms of the NLRP1, NLRP3, IPAF, and AIM2 inflammasomes are discussed. Regulatory mechanisms that potentiate or limit inflammasome activation are examined, as well as emerging links between the inflammasome and pyroptosis and autophagy. 2010 Elsevier Inc. All rights reserved.
                Bookmark

                Author and article information

                Journal
                Kidney Dis (Basel)
                Kidney Dis (Basel)
                KDD
                KDD
                Kidney Diseases
                S. Karger AG (Basel, Switzerland )
                2296-9381
                2296-9357
                24 June 2023
                December 2023
                : 9
                : 6
                : 443-458
                Affiliations
                [1]Department of Clinical Pharmacy, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
                Author notes
                Correspondence to: Qin Li, liqin0626@ 123456hotmail.com
                Article
                531642
                10.1159/000531642
                10712988
                38089443
                3d07234a-b72f-4705-a4b9-f37093250d15
                © 2023 The Author(s). Published by S. Karger AG, Basel

                This article is licensed under the Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC) ( http://www.karger.com/Services/OpenAccessLicense). Usage and distribution for commercial purposes requires written permission.

                History
                : 18 January 2023
                : 12 June 2023
                : 2023
                Page count
                Figures: 4, Tables: 2, References: 152, Pages: 16
                Funding
                No funding agency granted the present study.
                Categories
                Review Article

                kidney diseases,pyroptosis,inflammation,programmed cell death,therapeutic drugs

                Comments

                Comment on this article