Role of the inflammasome, gasdermin D, and pyroptosis in non‐alcoholic fatty liver disease

Abstract

Pyroptosis is a type of programmed cell death mediated by a multiprotein complex called the inflammasome through the pro-inflammatory activity of gasdermin D. This study aimed to recognize the final biological product that leads to pore formation in the cell membrane, lysis, pro-inflammatory cytokines release, and the establishment of an immune response. An exhaustive search engine investigation of an elevated immune response can induce a sustained inflammation that directly links this mechanism to non-alcoholic fatty liver disease and its progression to non-alcoholic steatohepatitis. Clinical studies and systematic reviews suggest that gasdermin D is a critical molecule between the immune response and the disease manifestation, which could be considered a therapeutic target for highly prevalent diseases characterized by presenting perpetuated inflammatory processes. Both basic and clinical research show evidence on the expression and regulation of the inflammasome-gasdermin D-pyroptosis trinomial for the progression of non-alcoholic fatty liver disease to non-alcoholic steatohepatitis.publication elsewhere, in whole or in part. We have not had any competing financial interests or commercial relationships that might pose a conflict of interest regarding the submitted manuscript. In case of acceptance, the copyright is transferred to the Journal of Gastroenterology and Hepatology. Author contribution: All authors have contributed to the article's development and improvement; they also agreed on the manuscript's content. Itzayana Rodríguez-Antonio, Guillermo N. López-Sánchez, and Natalia Nuño-Lámbarri designed and wrote the article. Norberto C. Chávez-Tapia and Misael Uribe reviewed, contributed various ideas, and corrected the manuscript's final version.Financial support: This research did not receive any specific grants from funding agencies in the public, commercial, or nonprofit sectors.

Hyperlipidemia May Synergize with Hypomethylation in Establishing Trained Immunity and Promoting Inflammation in NASH and NAFLD

“…It has been reported that caspase-11 mediates hepatocyte pyroptosis and promotes the progression of MCD diet-induced NASH/NAFLD [ 80 ]; and inflammasome-gasdermin D-pyroptosis [ 81 ] may regulate the progression of NASH/NAFLD [ 82 ]. In addition to promoting inflammation by enzymatic cleavage of pre-IL-1 β , pre-IL-18, and N-terminal GSDMD, caspase-1 also cleaves as many as 114 substrates, suggesting that caspase-1 may regulate inflammation indirectly via all the protein substrate-mediated signaling [ 15 ], 38 interaction protein-mediated signaling [ 15 ], and GSDMD-secretome-mediated signaling [ 23 ].…”

Pyroptosis patterns and immune infiltrates characterization in head and neck squamous cell carcinoma

“…Based on literature mining, 21 , 22 , 23 , 24 a total of 33 genes that were related to pyroptosis were identified (Table S1 ). The expression of 33 PRGs was extracted and compared between 502 HNSCC and 44 normal samples using the “limma” and “pheatmap” package from TCGA‐HNSC cohort.…”

Multi‐faceted role of pyroptosis mediated by inflammasome in liver fibrosis

“…Liver is composed of a variety of cells including hepatocytes and nonparenchymal cells. In addition to the cells described in this review, inflammasome is also expressed in liver sinusoidal endothelial cells, myofibroblasts, dendritic cells, neutrophils and other cells in liver 68 …”

“…In addition to the cells described in this review, inflammasome is also expressed in liver sinusoidal endothelial cells, myofibroblasts, dendritic cells, neutrophils and other cells in liver. 68 These cells all participant in the process of liver injury, but whether they can induce pyroptotic cell death to regulate liver inflammation and fibrosis is still unknown and needs further investigation.…”