Hepatic HRC induces hepatocyte pyroptosis and HSCs activation via NLRP3/caspase-1 pathway

Wu, Jingwen; Zhang, Mingyu; Xia, Suhong; Han, Ping; Zhao, Kai; Peng, Kaixin; Zhou, Wangdong; Tian, Dean; Liao, Jiazhi; Liu, Jingmei

doi:10.1007/s00109-022-02270-8

Cited by 4 publications

(6 citation statements)

References 41 publications

(27 reference statements)

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“… 41 , 42 Furthermore, dying hepatocytes induced by pyroptosis can release HMGB1, which promotes HSC activation. 43 Suppression of hepatocyte pyroptosis is found to reduce liver fibrosis. 44 , 45 …”

Section: Pcd Participates In the Pathogenesis Of Liver Fibrosismentioning

confidence: 99%

Programmed Cell Death in Liver Fibrosis

Gao,

Tang,

Mao

2023

JIR

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Programmed cell death (PCD) is a comprehensive term that encompasses various forms of cell death, such as apoptosis, necroptosis, pyroptosis, ferroptosis, and autophagy, which play a crucial role in the pathogenesis of liver fibrosis. PCD facilitates the elimination of aberrant cells, particularly activated hepatic stellate cells (HSCs), which are the primary producers of extracellular matrix (ECM). The removal of HSCs may impede ECM synthesis, thereby mitigating liver fibrosis. As such, PCD has emerged as a promising therapeutic target for the development of novel drugs to treat liver fibrosis. Numerous studies have been conducted to investigate the underlying mechanisms of PCD in the elimination of activated HSCs and other aberrant liver cells in fibrotic liver tissue, including hepatocytes, hepatic sinusoid endothelial cells (LSECs), and Kupffer cells (KCs). The induction of PCD, the interplay between different forms of PCD, and the potential harm or benefit of PCD in liver fibrosis are topics of ongoing research. Evidences suggest that PCD is a complex process with dual effects on liver fibrosis. The purpose of this review is to summarize the most recent advances in PCD and liver fibrosis research.

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Section: Pcd Participates In the Pathogenesis Of Liver Fibrosismentioning

confidence: 99%

Programmed Cell Death in Liver Fibrosis

Gao,

Tang,

Mao

2023

JIR

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“…Similarly, NLRP3 activation promotes HF. In humans with HF and CCL 4 ‐induced mouse models of HF, Wu et al (2022) found that the histidine‐rich calcium‐binding protein, a homeostatic regulator of Ca 2+ , activates NLRP3 inflammasomes and induces pyroptosis via the NLRP3/caspase‐1 pathway. The subsequent release of the DAMP molecule HMGB1 then promotes the activation of HSCs, which leads to or exacerbates extracellular matrix protein synthesis and deposition and subsequently promotes HF (Xie et al, 2022).…”

Section: Liver Diseases and Pyroptosismentioning

confidence: 99%

“…The subsequent release of the DAMP molecule HMGB1 then promotes the activation of HSCs, which leads to or exacerbates extracellular matrix protein synthesis and deposition and subsequently promotes HF (Xie et al, 2022). Moreover, the NLRP3 inhibitor MCC950 and the caspase‐1 inhibitor VX‐765 attenuate histidine‐rich calcium‐binding protein‐mediated pyroptosis and HSC activation, which in turn attenuate HF (Wu et al, 2022). Irisin inhibits reactive oxygen species (ROS) overexpression and NLRP3 inflammasome activation, thereby suppressing or improving the inflammatory response and reducing sepsis‐induced LI (Li, Tan, et al, 2021).…”

Section: Liver Diseases and Pyroptosismentioning

confidence: 99%

“…It has been shown that in ALD models, alcohol can stimulate thioredoxin-interacting protein (TXNIP) overexpression by regulating microRNA-148a (miR-148a), thereby inducing NLRP3 activation, causing pyroptosis, and exacerbating liver injury (LI; Heo et al, 2019). In a model of HF, pyroptosis could accelerate the formation of fibrous scars by promoting hepatic stellate cell (HSC) activation and exacerbating extracellular matrix deposition (Wu et al, 2022). All-trans-retinoic acid triggered ALI by activating NLRP3 and inducing pyroptosis (Yu et al, 2022).…”

Section: Liver Diseases and Pyroptosismentioning

confidence: 99%

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Recent advances in pyroptosis, liver disease, and traditional Chinese medicine: A review

He,

Xu,

Mao

et al. 2023

Phytotherapy Research

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In recent years, the incidence of liver disease has increased, becoming a major cause of death. Various liver diseases are intricately linked to pyroptosis, which is one of the most common forms of programmed cell death. As a powerful weapon in the fight against liver diseases, traditional Chinese medicine (TCM) can affect pyroptosis via a number of routes, including the classical, nucleotide oligomerization domain‐like receptors protein 3/caspase‐1/gasdermin D (GSDMD) pathway, the nonclassical lipopolysaccharide/caspase‐11/GSDMD pathway, the ROS/caspase‐3/gasdermin E pathway, the caspase‐9/caspase‐3/GSDMD pathway, and the Apaf‐1/caspase‐11/caspase‐3 pathway. In this review, we provide an overview of pyroptosis, the interplay between pyroptosis and liver diseases, and the mechanisms through which TCM regulates pyroptosis in liver diseases. The information used in the text was collected and compiled from the databases of PubMed, Web of Science, Scopus, CNKI, and Wanfang Data up to June 2023. The search was not limited with regard to the language and country of the articles. Research and review articles were included, and papers with duplicate results or unrelated content were excluded. We examined the current understanding of the relationship between pyroptosis and liver diseases as well as the advances in TCM interventions to provide a resource for the identification of potential targets for TCM in the treatment of liver diseases.

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“…The activation of NLRP3 inflammasome prompts ASC to recruit pro-caspase-1, leading to the auto-catalytic activation of caspase-1, and the cleaved caspase-1 cleaves GSDMD into the N-terminal domain of GSDMD (GSDMD-N) and forms pores on the plasma membrane to facilitate the maturation and release of IL-1β and IL-18, thereby causing pyroptosis [ 18 , 19 ]. Proir studies have demonstrated that supression of the NLRP3/Caspase-1 pathway can not only significantly inhibit the formation of fibrosis after acute kidney injury, but also induce hepatocyte pyroptosis to curb hepatocyte fibrosis [ 20 , 21 ], indicating that the NLRP3/caspase-1 axis-mediated pyroptosis is closely bound up with the process of cell fibrosis. Moreover, NaB impedes high glucose-induced NLRP3 overexpression in human monocyte macrophage THP-1 cells, negatively regulates NLRP3-mediated inflammatory signaling pathways, suppresses macrophage activation and secretion of pro-inflammatory mediators (such as IL-18 and IL-1β), reduces intestinal inflammation level, and limits colitis-associated cancer development [ 22 , 23 ].…”

Section: Introductionmentioning

confidence: 99%

Mechanism of sodium butyrate, a metabolite of gut microbiota, regulating cardiac fibroblast transdifferentiation via the NLRP3/Caspase-1 pyroptosis pathway

Dong,

Huang,

Jin

2024

J Cardiothorac Surg

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Background Cardiac fibroblasts (CFs) are activated after initial injury, and then differentiate into myofibroblasts (MFs), which play a pivotal role as the primary mediator cells in pathological remodeling. Sodium butyrate (NaB), being a metabolite of gut microbiota, exhibits anti-inflammatory property in local therapies on sites other than the intestine. Thus, this study aimed to probe the mechanism by which NaB regulates CFs transdifferentiation through the NLRP3/Caspase-1 pyroptosis pathway. Methods CFs were cultured in vitro and induced into MFs by TGFβ1. CFs were identified by immunofluorescence labelling technique of vimentin and α-SMA, followed by treatment with NaB or NLRP3 inflammasome inhibitor (CY-09) and its activator [nigericin sodium salt (NSS)]. The expression levels of α-SMA, GSDMD-N/NLRP3/cleaved Caspase-1 proteins, and inflammatory factors IL-1β/IL-18/IL-6/IL-10 were determined using immunofluorescence, Western blot and ELISA. Cell proliferation and migration were evaluated using the CCK-8 assay and the cell scratch test, respectively. Results Following the induction of TGFβ1, CFs exhibited increased expression levels of α-SMA proteins and IL-6/IL-10, as well as cell proliferative and migratory abilities. TGFβ1 induced CFs to differentiate into MFs, while NaB inhibited this differentiation. NaB inactivated the NLRP3/Caspase-1 pyroptosis pathway. CY-09 demonstrated inhibitory effects on the NLRP3/Caspase-1 pyroptosis pathway, leading to a reduction in TGFβ1-induced CFs transdifferentiation. NSS activated the NLRP3/Caspase-1 pyroptosis pathway, and thus partially counteracting the inhibitory effect of intestinal microbiota metabolite NaB on CFs transdifferentiation. Conclusion NaB, a metabolite of the gut microbiota, inhibited the activation of the NLRP3/Caspase-1 pyroptosis pathway in TGFβ1-induced CFs, repressed the transdifferentiation of CFs into MFs.

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Hepatic HRC induces hepatocyte pyroptosis and HSCs activation via NLRP3/caspase-1 pathway

Cited by 4 publications

References 41 publications

Programmed Cell Death in Liver Fibrosis

Programmed Cell Death in Liver Fibrosis

Recent advances in pyroptosis, liver disease, and traditional Chinese medicine: A review

Mechanism of sodium butyrate, a metabolite of gut microbiota, regulating cardiac fibroblast transdifferentiation via the NLRP3/Caspase-1 pyroptosis pathway

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