Pyroptosis in Steatohepatitis and Liver Diseases

Knorr, Jana; Wree, Alexander; Feldstein, Ariel E.

doi:10.1016/j.jmb.2021.167271

Cited by 25 publications

(14 citation statements)

References 121 publications

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“…Pyroptosis, as a form of lytic cell death, is observed in chronic liver diseases such as ALD and MASLD/metabolic dysfunction-associated steatohepatitis (MASH) [ 5 ]. Pyroptotic cell death leads to the release of proinflammatory cytokines and cellular lysis.…”

Section: Types Of Cell Deathmentioning

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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Section: Types Of Cell Deathmentioning

confidence: 99%

Cell Death in Liver Disease and Liver Surgery

Stoess,

Choi,

Onyuru

et al. 2024

Biomedicines

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“…Ferroptosis is a type of RCD sensitive to iron accumulation which is then executed by glutathione peroxidase 4 (GPx4) deletion and subsequently overwhelming lipid peroxidation, while pyroptosis a lytic form triggered by invasive pathogens/tissue injury to amplify inflammation. Both described RCD modalities are involved in the pathogenesis of various liver diseases (Refs 104, 105). In this context, the interplay between RCD and septic liver injury has been concerns of scientific endeavour.…”

Section: Infection-associated Liver Injurymentioning

confidence: 99%

The potential role of FNDC5/irisin in various liver diseases: awakening the sleeping beauties

Wang

Mao²,

Li³

et al. 2022

Expert Rev. Mol. Med.

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Fibronectin type III domain-containing protein 5 (FNDC5) is a transmembrane protein and the precursor of irisin, which serves as a systemic exerkine/myokine with multiple origins. Since its discovery in 2012, this hormone-like polypeptide has rapidly evolved to a component significantly involved in a gamut of metabolic dysregulations and various liver diseases. After a decade of extensive investigation on FNDC5/irisin, we are still surrounded by lots of open questions regarding its diagnostic and therapeutic values. In this review, we first concentrated on the structure–function relationship of FNDC5/irisin. Next, we comprehensively summarised the current knowledge and research findings regarding pathogenic roles/therapeutic applications of FNDC5/irisin in the context of non-alcoholic fatty liver disease, fibrosis, liver injury due to multiple detrimental insults, hepatic malignancy and intrahepatic cholestasis of pregnancy. Moreover, the prominent molecules involved in the underlying mechanisms and signalling pathways were highlighted. As a result, emerging evidence reveals FNDC5/irisin may act as a proxy for diagnosing liver disease pathology, a sensitive biomarker for assessing damage severity, a predisposing factor for surveilling illness progression and a treatment option with protective/preventive impact, all of which are highly dependent on disease grading and contextually pathological features.

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“…Hence, pyroptosis needs to be strictly managed. 2 During the process of pyroptosis, the nucleotide binding oligomerization domain like receptor protein 3 (NLRP3) forms inflammasomes that convert pro-caspase-1 to activated caspase-1, then promote the maturation of interleukin-1β (IL-1β) and interleukin-18 (IL-18) precursors and finally mediate pyroptosis, which is critical for the initiation and maintenance of inflammatory reactions. 3,4 Additionally, gas-dermin D (GSDMD), as an effector protein that forms pores, is cleaved by activated caspase-1 into the GSDMD-N-terminal domain (GSDMD-N).…”

Section: Introductionmentioning

confidence: 99%