Research Progress of Pyroptosis in Fatty Liver Disease

Li, Rongxuan; Xue, Weiyue; Wei, Huiting; Fan, Qingqing; Li, Xiang; Qiu, Ye; Cui, Di

doi:10.3390/ijms241713065

Cited by 7 publications

(5 citation statements)

References 99 publications

(145 reference statements)

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“…Figure 5 shows the scheme of hepatocyte protection from ferroptosis due to MSC and MSC derivatives. Recent studies have shown that inflammasome-mediated pyroptosis is a driver of inflammation and plays a critical role in the progression of liver pathologies, such as autoimmune liver diseases [238], liver fibrosis [239], and fatty liver diseases [240,241]. Therefore, pharmacological pyroptosis targeting may become an option for reducing inflammation in liver diseases.…”

Section: Anti-ferroptosis and Anti-pyroptosis Effects Of Mscmentioning

confidence: 99%

The Crosstalk between Mesenchymal Stromal/Stem Cells and Hepatocytes in Homeostasis and under Stress

Kholodenko,

Yarygin

2023

IJMS

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Liver diseases, characterized by high morbidity and mortality, represent a substantial medical problem globally. The current therapeutic approaches are mainly aimed at reducing symptoms and slowing down the progression of the diseases. Organ transplantation remains the only effective treatment method in cases of severe liver pathology. In this regard, the development of new effective approaches aimed at stimulating liver regeneration, both by activation of the organ’s own resources or by different therapeutic agents that trigger regeneration, does not cease to be relevant. To date, many systematic reviews and meta-analyses have been published confirming the effectiveness of mesenchymal stromal cell (MSC) transplantation in the treatment of liver diseases of various severities and etiologies. However, despite the successful use of MSCs in clinical practice and the promising therapeutic results in animal models of liver diseases, the mechanisms of their protective and regenerative action remain poorly understood. Specifically, data about the molecular agents produced by these cells and mediating their therapeutic action are fragmentary and often contradictory. Since MSCs or MSC-like cells are found in all tissues and organs, it is likely that many key intercellular interactions within the tissue niches are dependent on MSCs. In this context, it is essential to understand the mechanisms underlying communication between MSCs and differentiated parenchymal cells of each particular tissue. This is important both from the perspective of basic science and for the development of therapeutic approaches involving the modulation of the activity of resident MSCs. With regard to the liver, the research is concentrated on the intercommunication between MSCs and hepatocytes under normal conditions and during the development of the pathological process. The goals of this review were to identify the key factors mediating the crosstalk between MSCs and hepatocytes and determine the possible mechanisms of interaction of the two cell types under normal and stressful conditions. The analysis of the hepatocyte–MSC interaction showed that MSCs carry out chaperone-like functions, including the synthesis of the supportive extracellular matrix proteins; prevention of apoptosis, pyroptosis, and ferroptosis; support of regeneration; elimination of lipotoxicity and ER stress; promotion of antioxidant effects; and donation of mitochondria. The underlying mechanisms suggest very close interdependence, including even direct cytoplasm and organelle exchange.

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Section: Anti-ferroptosis and Anti-pyroptosis Effects Of Mscmentioning

confidence: 99%

The Crosstalk between Mesenchymal Stromal/Stem Cells and Hepatocytes in Homeostasis and under Stress

Kholodenko,

Yarygin

2023

IJMS

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“…Likewise, cleavage at D36 of pro-IL-18 generates an 18 kDa mature protein from its 23 kDa pro-form, which possesses enhanced inflammatory property. The aftermath of caspase-1 cleavage is not just the maturation of IL-1 cytokines but also cleavage of gasdermin D [14]. Cleavage of gasdermin D results in translocation of its N-terminal fraction into the plasma membrane to cause pore formation.…”

Section: Introductionmentioning

confidence: 99%

Mechanisms of Inflammasome Activation and Involvement in Liver Disease

Baral

2024

JMP

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The liver is a multi-potent organ with important metabolic, immunological and endocrine functions. Hepatic physiology is maintained at a balanced state via the delicate actions of different liver-resident cells. Among several factors that modulate hepatic physiology, the harmony between the activity of pro- and anti-inflammatory cytokines is a crucial determinant. However, initiation of inflammatory activity can be detrimental if it goes unresolved, leading to severe consequences such as hepatitis, hepatic fibrosis, cirrhosis or even hepatocellular carcinoma (HCC). Different physiological processes can modulate the hepatic microenvironment; one such factor is a cytosolic protein complex called the inflammasome. Inflammasome activation is a consequence of the cellular encounter with pathogens or products of cellular damage. Once activated, inflammasomes promote the maturation of interleukin-1 family cytokines such as IL-1β and IL-18 via activation of caspase-1. These cytokines have a very potent role in modulating hepatic physiology. Various lines of reports suggest that inflammasome activation and IL-1 cytokines play critical roles in liver diseases, including hepatitis, hepatic fibrosis and HCC. Conversely, inhibition of inflammasome activation and/or IL-1 signaling prevents such effects. This review summarizes the mechanisms leading to inflammasome activation and the role it plays in hepatic physiology.

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“…Current research indicates that the pathogenesis of NAFLD is complex, with steatosis, lipotoxicity, and inflammatory responses playing critical roles ( Cobbina and Akhlaghi, 2017 ). Recent studies have underscored the importance of pyroptosis, a specific type of cell death, as a pivotal element in modulating inflammation and immune responses ( Yu et al, 2021 ; Li et al, 2023 ). Feng et al 2022) observed that upregulation of phosphorylated STAT3 promotes Anxa2 expression at the transcriptional level, thereby activating caspase-1-mediated hepatocyte pyroptosis and fibrosis in NASH.…”

Section: Introductionmentioning

confidence: 99%

The role and mechanism of pyroptosis and potential therapeutic targets in non-alcoholic fatty liver disease (NAFLD)

Li,

Liu,

et al. 2024

Front. Cell Dev. Biol.

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Non-alcoholic fatty liver disease (NAFLD) is a clinical pathological syndrome characterized by the excessive accumulation of fat within liver cells, which can progress to end-stage liver disease in severe cases, posing a threat to life. Pyroptosis is a distinct, pro-inflammatory form of cell death, differing from traditional apoptosis. In recent years, there has been growing research interest in the association between pyroptosis and NAFLD, encompassing the mechanisms and functions of pyroptosis in the progression of NAFLD, as well as potential therapeutic targets. Controlled pyroptosis can activate immune cells, eliciting host immune responses to shield the body from harm. However, undue activation of pyroptosis may worsen inflammatory responses, induce cellular or tissue damage, disrupt immune responses, and potentially impact liver function. This review elucidates the involvement of pyroptosis and key molecular players, including NOD-like receptor thermal protein domain associated protein 3(NLRP3) inflammasome, gasdermin D (GSDMD), and the caspase family, in the pathogenesis and progression of NAFLD. It emphasizes the promising prospects of targeting pyroptosis as a therapeutic approach for NAFLD and offers valuable insights into future directions in the field of NAFLD treatment.

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Research Progress of Pyroptosis in Fatty Liver Disease

Cited by 7 publications

References 99 publications

The Crosstalk between Mesenchymal Stromal/Stem Cells and Hepatocytes in Homeostasis and under Stress

The Crosstalk between Mesenchymal Stromal/Stem Cells and Hepatocytes in Homeostasis and under Stress

Mechanisms of Inflammasome Activation and Involvement in Liver Disease

The role and mechanism of pyroptosis and potential therapeutic targets in non-alcoholic fatty liver disease (NAFLD)

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