Stress kinases in the development of liver steatosis and hepatocellular carcinoma

Cicuéndez, Beatriz; Ruiz-Garrido, Irene; Mora, Alfonso; Sabio, Guadalupe

doi:10.1016/j.molmet.2021.101190

Cited by 30 publications

(23 citation statements)

References 218 publications

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“…To this end, we here found that the silencing of MAP4K4 markedly lowered both JNK and ERK phosphorylation level in human hepatocytes. This observation is interesting in the light of recent reports revealing that activation of hepatic JNK and ERK pathways mediates NAFLD initiation and aggravation; however, the underlying mechanisms have remained largely elusive (46,47,(62)(63)(64). In all, it is plausible that alterations in JNK and ERK signaling may constitute an important part of the mode-of-action of MAP4K4 in the control of NAFLD susceptibility.…”

Section: Changes In Extracellular Signal Erk Jnk and Akt Signaling Ac...mentioning

confidence: 83%

Inhibition of MAP4K4 signaling initiates metabolic reprogramming to protect hepatocytes from lipotoxic damage

Anand¹,

Caputo²,

Xia³

et al. 2022

Journal of Lipid Research

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Section: Changes In Extracellular Signal Erk Jnk and Akt Signaling Ac...mentioning

confidence: 83%

Inhibition of MAP4K4 signaling initiates metabolic reprogramming to protect hepatocytes from lipotoxic damage

Anand¹,

Caputo²,

Xia³

et al. 2022

Journal of Lipid Research

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“…Even more problematic is the fact that there is currently no effective treatment for NASH-related hepatocellular carcinoma (HCC) [ 4 ]. However, the factors influencing the progression from NAFLD to NASH and even to HCC are unclear; although, multiple hypotheses have been proposed, including lipotoxicity, oxidative stress, and proinflammatory mediators [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Identification of Key Genes and Immune Infiltrate in Nonalcoholic Steatohepatitis: A Bioinformatic Analysis

Jiang

Zhou

et al. 2021

BioMed Research International

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Background. Nonalcoholic steatohepatitis (NASH) can progress to cirrhosis and hepatic carcinoma and is closely associated with changes in the neurological environment. The discovery of new biomarkers would aid in the treatment of NASH. Methods. Data GSE89632 were downloaded from the Gene Expression Omnibus (GEO) database, and R package “limma” was used to identify differentially expressed genes (DEGs) for NASH vs. normal tissues. The STRING database was used to construct a protein-protein interaction (PPI) network, and the Cytoscape software program (Version 3.80) was used to visualize the PPI network and identify key genes. The immune infiltration of NASH was determined using the R package “CIBERSORT”. Results. We screened 41 DEGs. GO and KEGG enrichment analyses of the DEGs revealed the enrichment of pathways related to NAFLD steatosis and inflammation. A PPI network analysis was also performed on the DEGs, and seven genes (MYC, CXCL8, FOS, SOCS1, SOCS3, IL6, and PTGS2) were identified as hub genes. An immune infiltration assessment revealed that macrophages M2, memory resting CD4+ T cells, and γΔ T cells play important roles in the immune microenvironment of NASH, which may be mediated by the seven identified hub genes.

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“…This nding suggests that both Firmicutes and Fusobacteria might exert desirable effects on NAFLD. MAPK inhibition attenuates obesity, insulin resistance, and steatosis in NAFLD [59]. With the highest degree of value of the metabolites of the gut microbiota, phenylacetylglutamine might be a biomarker to sign hepatic dysfunction [60].…”

Section: Discussionmentioning

confidence: 99%

Exploration of metabolites from gut microbiota against nonalcoholic fatty liver disease: A network pharmacology-based study

Gupta

Min

et al. 2022

Preprint

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Background: The metabolites of gut microbiota show favorable therapeutic effects on nonalcoholic fatty liver disease (NAFLD), but the active metabolites and mechanisms against NAFLD have not been documented. The aim of the study was to investigate the active metabolites and mechanisms of gut microbiota against NAFLD by network pharmacology. Results: We obtained a total of 208 metabolites from the gutMgene database and retrieved 1,256 targets from similarity ensemble approach (SEA) and 947 targets from the SwissTargetPrediction (STP) database. In the SEA and STP databases, we identified 668 overlapping targets and obtained 237 targets for NAFLD. Thirty-eight targets were identified out of those 237 and 223 targets retrieved from the gutMgene database, and were considered the final NAFLD targets of metabolites from the microbiome. The results of molecular docking tests suggest that, of the 38 targets, mitogen-activated protein kinase 8-compound K and glycogen synthase kinase-3 beta-myricetin complexes might inhibit the Wnt signaling pathway. The microbiota-signaling pathways-targets-metabolites network analysis reveals that Firmicutes, Fusobacteria, the Toll-like receptor signaling pathway, mitogen-activated protein kinase 1, and phenylacetylglutamine are notable components of NAFLD.Conclusion: The key components and potential mechanisms of metabolites from gut microbiota against NAFLD were explored utilizing network pharmacology analyses. This study provides scientific evidence to support the therapeutic efficacy of metabolites for NAFLD and suggests holistic insights for further research.

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Stress kinases in the development of liver steatosis and hepatocellular carcinoma

Cited by 30 publications

References 218 publications

Inhibition of MAP4K4 signaling initiates metabolic reprogramming to protect hepatocytes from lipotoxic damage

Inhibition of MAP4K4 signaling initiates metabolic reprogramming to protect hepatocytes from lipotoxic damage

Identification of Key Genes and Immune Infiltrate in Nonalcoholic Steatohepatitis: A Bioinformatic Analysis

Exploration of metabolites from gut microbiota against nonalcoholic fatty liver disease: A network pharmacology-based study

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