Mechanisms of NLRP3 inflammasome-mediated hepatic stellate cell activation: Therapeutic potential for liver fibrosis
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 o...
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| Format: | Article |
| Language: | English |
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KeAi Communications Co., Ltd.
2023-03-01
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| Series: | Genes and Diseases |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352304221001707 |
| _version_ | 1797699781930254336 |
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| author | Harsh Vardhan Charan Durgesh Kumar Dwivedi Sabbir Khan Gopabandhu Jena |
| author_facet | Harsh Vardhan Charan Durgesh Kumar Dwivedi Sabbir Khan Gopabandhu Jena |
| author_sort | Harsh Vardhan Charan |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-12T04:13:49Z |
| format | Article |
| id | doaj.art-52193506f2514a1885e695bd25189227 |
| institution | Directory Open Access Journal |
| issn | 2352-3042 |
| language | English |
| last_indexed | 2024-03-12T04:13:49Z |
| publishDate | 2023-03-01 |
| publisher | KeAi Communications Co., Ltd. |
| record_format | Article |
| series | Genes and Diseases |
| spelling | doaj.art-52193506f2514a1885e695bd251892272023-09-03T10:49:15ZengKeAi Communications Co., Ltd.Genes and Diseases2352-30422023-03-01102480494Mechanisms of NLRP3 inflammasome-mediated hepatic stellate cell activation: Therapeutic potential for liver fibrosisHarsh Vardhan Charan0Durgesh Kumar Dwivedi1Sabbir Khan2Gopabandhu Jena3Facility 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 160062, IndiaFacility 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 160062, IndiaFacility 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 160062, India; Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USAFacility 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 160062, India; Corresponding author. Fax: +91 172 221469.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.http://www.sciencedirect.com/science/article/pii/S2352304221001707Hepatic stellate cellsLiver fibrosisNLRP3 activationNLRP3 inflammasomeNLRP3 inhibitors |
| spellingShingle | Harsh Vardhan Charan Durgesh Kumar Dwivedi Sabbir Khan Gopabandhu Jena Mechanisms of NLRP3 inflammasome-mediated hepatic stellate cell activation: Therapeutic potential for liver fibrosis Genes and Diseases Hepatic stellate cells Liver fibrosis NLRP3 activation NLRP3 inflammasome NLRP3 inhibitors |
| title | Mechanisms of NLRP3 inflammasome-mediated hepatic stellate cell activation: Therapeutic potential for liver fibrosis |
| title_full | Mechanisms of NLRP3 inflammasome-mediated hepatic stellate cell activation: Therapeutic potential for liver fibrosis |
| title_fullStr | Mechanisms of NLRP3 inflammasome-mediated hepatic stellate cell activation: Therapeutic potential for liver fibrosis |
| title_full_unstemmed | Mechanisms of NLRP3 inflammasome-mediated hepatic stellate cell activation: Therapeutic potential for liver fibrosis |
| title_short | Mechanisms of NLRP3 inflammasome-mediated hepatic stellate cell activation: Therapeutic potential for liver fibrosis |
| title_sort | mechanisms of nlrp3 inflammasome mediated hepatic stellate cell activation therapeutic potential for liver fibrosis |
| topic | Hepatic stellate cells Liver fibrosis NLRP3 activation NLRP3 inflammasome NLRP3 inhibitors |
| url | http://www.sciencedirect.com/science/article/pii/S2352304221001707 |
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