12
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Involvement of Nucleotide-Binding Oligomerization Domain-Like Receptor Family Pyrin Domain Containing 3 Inflammasome in the Pathogenesis of Liver Diseases

      review-article

      Read this article at

      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

          The inflammasome is widely acknowledged for its crucial role in the pathogenesis of cancers and many neurodegenerative, metabolic, and auto-inflammatory diseases in recent years. Multiple types of inflammasomes exist. However, nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasome is the most often investigated inflammasome and has come to limelight in recent studies. NLRP3 inflammasome is a multi-protein complex. Its activation can cause the cleavage of inactive pro-caspase-1 into activated caspase-1, that ultimately promotes the transformation of pro-interleukin (IL)-1β and pro-IL-18 into biologically-active IL-1β and IL-18, respectively. These processes lead to the local inflammatory responses and induce pyroptosis, causing disparaging effects. Recently, numerous studies have shown that NLRP3 inflammasome plays an important role in the pathogenesis of liver diseases, including non-alcoholic fatty liver disease, liver fibrosis, cirrhosis, and hepatocellular carcinoma. Liver diseases have become a severe health burden worldwide, and there is adequate evidence indicating that the regulation of NLRP3 inflammasome acts as a guard against hazard to liver. In this review, we provide a straightforward overview of NLRP3 inflammasome as well as several frequent liver diseases. We then discuss the contribution and regulation of NLRP3 inflammasome during the pathogenesis of liver diseases, which may provide an important indication for the prevention and treatment of various liver diseases.

          Related collections

          Most cited references55

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

          The NLRP3 inflammasome: molecular activation and regulation to therapeutics

          NLRP3 (NACHT, LRR and PYD domains-containing protein 3) is an intracellular sensor that detects a broad range of microbial motifs, endogenous danger signals and environmental irritants, resulting in the formation and activation of the NLRP3 inflammasome. Assembly of the NLRP3 inflammasome leads to caspase-1-dependent release of the proinflammatory cytokines, IL-1β and IL-18, as well as to gasdermin D-mediated pyroptotic cell death. Recent studies have revealed new regulators of the NLRP3 inflammasome, including new interacting or regulatory proteins, metabolic pathways and a regulatory mitochondrial hub. In this Review, we present the molecular, cell biological and biochemical basis of NLRP3 activation and regulation, and describe how this mechanistic understanding is leading to potential therapeutics that target the NLRP3 inflammasome.
            Bookmark
            • Record: found
            • Abstract: not found
            • Article: not found

            Targeting the NLRP3 inflammasome in inflammatory diseases

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

              Pathobiology of liver fibrosis: a translational success story.

              Reversibility of hepatic fibrosis and cirrhosis following antiviral therapy for hepatitis B or C has advanced the prospect of developing antifibrotic therapies for patients with chronic liver diseases, especially non-alcoholic steatohepatitis. Mechanisms of fibrosis have focused on hepatic stellate cells, which become fibrogenic myofibroblasts during injury through 'activation', and are at the nexus of efforts to define novel drug targets. Recent studies have clarified pathways of stellate cell gene regulation and epigenetics, emerging pathways of fibrosis regression through the recruitment and amplification of fibrolytic macrophages, nuanced responses of discrete inflammatory cell subsets and the identification of the 'ductular reaction' as a marker of severe injury and repair. Based on our expanded knowledge of fibrosis pathogenesis, attention is now directed towards strategies for antifibrotic therapies and regulatory challenges for conducting clinical trials with these agents. New therapies are attempting to: 1) Control or cure the primary disease or reduce tissue injury; 2) Target receptor-ligand interactions and intracellular signaling; 3) Inhibit fibrogenesis; and 4) Promote resolution of fibrosis. Progress is urgently needed in validating non-invasive markers of fibrosis progression and regression that can supplant biopsy and shorten the duration of clinical trials. Both scientific and clinical challenges remain, however the past three decades of steady progress in understanding liver fibrosis have contributed to an emerging translational success story, with realistic hopes for antifibrotic therapies to treat patients with chronic liver disease in the near future.
                Bookmark

                Author and article information

                Contributors
                Journal
                Front Cell Dev Biol
                Front Cell Dev Biol
                Front. Cell Dev. Biol.
                Frontiers in Cell and Developmental Biology
                Frontiers Media S.A.
                2296-634X
                10 March 2020
                2020
                : 8
                : 139
                Affiliations
                Provincial Key Laboratory for Developmental Biology and Neurosciences, Key Laboratory of Optoelectronic Science and Technology for Medicine of Ministry of Education, College of Life Sciences, Fujian Normal University , Fuzhou, China
                Author notes

                Edited by: Yang Zhang, University of Houston, United States

                Reviewed by: Mi Wang, Huazhong University of Science and Technology, China; Mariateresa Giuliano, University of Campania Luigi Vanvitelli, Italy

                *Correspondence: Hongqin Yang, hqyang@ 123456fjnu.edu.cn

                This article was submitted to Molecular Medicine, a section of the journal Frontiers in Cell and Developmental Biology

                Article
                10.3389/fcell.2020.00139
                7075939
                32211410
                153215df-6a7e-4d36-a88c-e4c3406927c5
                Copyright © 2020 Shi, Yang and Zhang.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 03 December 2019
                : 19 February 2020
                Page count
                Figures: 3, Tables: 0, Equations: 0, References: 70, Pages: 8, Words: 0
                Categories
                Cell and Developmental Biology
                Review

                nlrp3 inflammasome,inflammation,non-alcoholic fatty liver disease,liver fibrosis,cirrhosis,hepatocellular carcinoma

                Comments

                Comment on this article