Mechanisms of NLRP3 inflammasome-mediated hepatic stellate cell activation: Therapeutic potential for liver fibrosis

Harsh Vardhan Charan; Durgesh Kumar Dwivedi; Sabbir Khan; Gopabandhu Jena

doi:10.1016/j.gendis.2021.12.006

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Mechanisms of NLRP3 inflammasome-mediated hepatic stellate cell activation: Therapeutic potential for liver fibrosis

Review article | 更新时间：2023-05-16

- Mechanisms of NLRP3 inflammasome-mediated hepatic stellate cell activation: Therapeutic potential for liver fibrosis
- Mechanisms of NLRP3 inflammasome-mediated hepatic stellate cell activation: Therapeutic potential for liver fibrosis
- Genes & Diseases 2023年10卷第2期
- 作者机构：
  
  1. Facility for Risk Assessment and Intervention Studies, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, Sector-67, S.A.S. Nagar, Punjab,India,160062
  2. Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center,TX,Houston,USA,77030
- 作者简介：
- 基金信息：
- DOI：10.1016/j.gendis.2021.12.006
  中图分类号：
- 纸质出版日期：2023，
  
  网络出版日期：2023-3-1，
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Mechanisms of NLRP3 inflammasome-mediated hepatic stellate cell activation: Therapeutic potential for liver fibrosis[J]. Genes & Diseases, 2023,10(2).

Harsh Vardhan Charan, Durgesh Kumar Dwivedi, Sabbir Khan, et al. Mechanisms of NLRP3 inflammasome-mediated hepatic stellate cell activation: Therapeutic potential for liver fibrosis[J]. Genes & Diseases, 2023,10(2).
Mechanisms of NLRP3 inflammasome-mediated hepatic stellate cell activation: Therapeutic potential for liver fibrosis[J]. Genes & Diseases, 2023,10(2). DOI： 10.1016/j.gendis.2021.12.006.

Harsh Vardhan Charan, Durgesh Kumar Dwivedi, Sabbir Khan, et al. Mechanisms of NLRP3 inflammasome-mediated hepatic stellate cell activation: Therapeutic potential for liver fibrosis[J]. Genes & Diseases, 2023,10(2). DOI： 10.1016/j.gendis.2021.12.006.

摘要

Abstract

The liver injury leads to an inflammatory response

which causes the activation of hepatic stellate cells (HSCs) that further secrete ECM proteins and play an important role in liver fibrosis. Moreover

the inflammatory response is a driving force for fibrogenesis

which is triggered by many types of injuries. Exaggerated inflammatory immune responses are mediated by cytoplasmic protein complexes known as inflammasomes

which are involved in many chronic liver diseases. Inflammasomes are pattern recognition receptors (PRRs) that can sense any microbial motifs known as pathogen-associated molecular patterns (PAMPs)

and host- or environmental-derived stress signals known as damage-associated molecular patterns (DAMPs). The inflammasomes cause caspase-mediated proteolytic cleavage of pro-IL-1β and pro-IL-18 into active IL-1β and IL-18. In this review

we provide a comprehensive summary of the important roles of NLRP3 inflammasome in the pathogenesis of liver fibrosis with an emphasis on several direct and indirect pathways responsible for the NLRP3 inflammasome-mediated HSCs activation and fibrogenesis. In addition

we discuss the general pharmacological and genetics strategies for the inhibition of NLRP3 inflammasome activation and its downstream signaling with examples of emerging pharmacotherapeutics

targeting the NLRP3 inflammasome signaling as well as a possible way to develop effective and safer NLRP3 inflammasome inhibitors.

关键词

Keywords

Hepatic stellate cellsLiver fibrosisNLRP3 activationNLRP3 inflammasomeNLRP3 inhibitors

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