Kupffer cell pyroptosis mediated by <scp>METTL3</scp> contributes to the progression of alcoholic steatohepatitis

Pan, Xuesheng; Li, Bowen; Wang, Lili; Li, N; Lin, Huimin; Zhang, Jin; Du, Na; Zhu, Yueqin; Wu, Xian; Hu, Chengmu; Wu, Wenhua; Hou, Hui; Zhao, Hua-Lu; Liao, Song-Yan; Yang, Yanan; Huang, Yan

doi:10.1096/fj.202300059rr

Cited by 11 publications

(4 citation statements)

References 30 publications

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“…Silencing the m6A enzyme methyltransferase-like 3 (METTL3) alleviates inflammatory factor release by repressing KC pyroptosis in ALD mice. This underscores the pivotal role of KC pyroptosis in ALD mice ( 83 ). Suppression of macrophages contributes to alleviating ALD-associated pathological damage.…”

Section: The Role Of Macrophage Pyroptosis In Liver Diseasesmentioning

confidence: 58%

Unveiling the flames: macrophage pyroptosis and its crucial role in liver diseases

Ni,

Chen,

Zhao

et al. 2024

Front. Immunol.

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Macrophages play a critical role in innate immunity, with approximately 90% of the total macrophage population in the human body residing in the liver. This population encompasses both resident and infiltrating macrophages. Recent studies highlight the pivotal role of liver macrophages in various aspects such as liver inflammation, regeneration, and immune regulation. A novel pro-inflammatory programmed cell death, pyroptosis, initially identified in macrophages, has garnered substantial attention since its discovery. Studies investigating pyroptosis and inflammation progression have particularly centered around macrophages. In liver diseases, pyroptosis plays an important role in driving the inflammatory response, facilitating the fibrotic process, and promoting tumor progression. Notably, the role of macrophage pyroptosis cannot be understated. This review primarily focuses on the role of macrophage pyroptosis in liver diseases. Additionally, it underscores the therapeutic potential inherent in targeting macrophage pyroptosis.

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Section: The Role Of Macrophage Pyroptosis In Liver Diseasesmentioning

confidence: 58%

Unveiling the flames: macrophage pyroptosis and its crucial role in liver diseases

Ni,

Chen,

Zhao

et al. 2024

Front. Immunol.

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“…When SIRT1 was knocked down, the protein expression of NLRP3, GSDMD, IL-1β, and IL-18 was significantly increased. 85 In addition, miR-148a levels were significantly reduced in patients with ALD and mouse models. Forkhead box protein O1 (FoxO1), as a transcription factor for miR-148a transcription activation, inhibits the expression of FoxO1 with alcohol and then reduces the expression of miR-148a.…”

Section: Nc-rna Mediated Pyroptosis Pathway In Ald and Nafldmentioning

confidence: 99%

NcRNA Regulated Pyroptosis in Liver Diseases and Traditional Chinese Medicine Intervention: A Narrative Review

Deng,

Qin,

Qin

et al. 2024

JIR

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Pyroptosis is a novel pro-inflammatory mode of programmed cell death that differs from ferroptosis, necrosis, and apoptosis in terms of its onset and regulatory mechanisms. Pyroptosis is dependent on cysteine aspartate protein hydrolase (caspase)-mediated activation of GSDMD, NLRP3, and the release of pro-inflammatory cytokines, interleukin-1 (IL-1β), and interleukin-18 (IL-18), ultimately leading to cell death. Non-coding RNA (ncRNA) is a type of RNA that does not encode proteins in gene transcription but plays an important regulatory role in other post-transcriptional links. NcRNA mediates pyroptosis by regulating various related pyroptosis factors, which we termed the pyroptosis signaling pathway. Previous researches have manifested that pyroptosis is closely related to the development of liver diseases, and is essential for liver injury, alcoholic fatty liver disease (ALD), non-alcoholic fatty liver disease (NAFLD), liver fibrosis, and liver cancer. In this review, we attempt to address the role of the ncRNA-mediated pyroptosis pathway in the above liver diseases and their pathogenesis in recent years, and briefly outline that TCM (Traditional Chinese Medicine) intervene in liver diseases by modulating ncRNA-mediated pyroptosis, which will provide a strategy to find new therapeutic targets for the prevention and treatment of liver diseases in the future.

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“…Pyroptosis activation in both hepatocytes and liver immune cells exacerbates liver inflammation through intercellular crosstalk. A recent study revealed that alcohol consumption induces pyroptosis in Kupffer cells, which release more IL-1β through active m6A enzyme methyltransferase-like 3 [ 101 ].…”

Section: Cell Death In Liver Diseasementioning

confidence: 99%

Cell Death in Liver Disease and Liver Surgery

Stoess,

Choi,

Onyuru

et al. 2024

Biomedicines

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Cell death is crucial for maintaining tissue balance and responding to diseases. However, under pathological conditions, the surge in dying cells results in an overwhelming presence of cell debris and the release of danger signals. In the liver, this gives rise to hepatic inflammation and hepatocellular cell death, which are key factors in various liver diseases caused by viruses, toxins, metabolic issues, or autoimmune factors. Both clinical and in vivo studies strongly affirm that hepatocyte death serves as a catalyst in the progression of liver disease. This advancement is characterized by successive stages of inflammation, fibrosis, and cirrhosis, culminating in a higher risk of tumor development. In this review, we explore pivotal forms of cell death, including apoptosis, pyroptosis, and necroptosis, examining their roles in both acute and chronic liver conditions, including liver cancer. Furthermore, we discuss the significance of cell death in liver surgery and ischemia-reperfusion injury. Our objective is to illuminate the molecular mechanisms governing cell death in liver diseases, as this understanding is crucial for identifying therapeutic opportunities aimed at modulating cell death pathways.

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Kupffer cell pyroptosis mediated by METTL3 contributes to the progression of alcoholic steatohepatitis

Cited by 11 publications

References 30 publications

Unveiling the flames: macrophage pyroptosis and its crucial role in liver diseases

Unveiling the flames: macrophage pyroptosis and its crucial role in liver diseases

NcRNA Regulated Pyroptosis in Liver Diseases and Traditional Chinese Medicine Intervention: A Narrative Review

Cell Death in Liver Disease and Liver Surgery

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