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Background

Tripartite motif containing proteins 23(TRIM23) is identified as an E3 ubiquitin ligase involved in signal transduction, but its role in liver fibrosis remains unknown.

Aims

To investigate the effects and mechanisms of TRIM23 on hepatic stellate cells(HSCs) ferroptosis and liver fibrosis.

Methods

We utilized the Gene Expression Omibus database to identify differentially expressed genes and downstream pathways. TRIM23 expression was examined in fibrotic liver tissues. The effects of TRIM23 on HSCs ferroptosis were validated through assessing cell viability, lipid peroxidation, and ferroptotic markers using HSC-T6 cell lines and primary rat HSCs. Co-immunoprecipitation assays were conducted to analyze the interactions between TRIM23 and p53. A CCl4-induced liver fibrosis rat model was employed to confirm the in vivo effects.

Results

TRIM23 expression was positively correlated with the severity of liver fibrosis. Upregulated TRIM23 expression promoted HSCs viability and activation by attenuating ferroptosis. Furthermore, the upregulation of TRIM23 expression significantly enhanced p53 ubiquitination. In contrast, TRIM23 knockdown induced HSCs ferroptosis by regulating p53, leading to the suppression of cell viability and activation. Silencing TRIM23 led to the regression of liver fibrosis induced by CCl4 treatment in vivo.

Conclusion

Our study uncovers a novel mechanism in which TRIM23 inhibits HSCs ferroptosis, promotes cell activation and contributes to liver fibrosis by regulating p53 ubiquitination."xsd:string
http://purl.uniprot.org/citations/37495427http://purl.org/dc/terms/identifier"doi:10.1016/j.dld.2023.07.010"xsd:string
http://purl.uniprot.org/citations/37495427http://purl.uniprot.org/core/author"Chen J."xsd:string
http://purl.uniprot.org/citations/37495427http://purl.uniprot.org/core/author"Li F."xsd:string
http://purl.uniprot.org/citations/37495427http://purl.uniprot.org/core/author"Lin S."xsd:string
http://purl.uniprot.org/citations/37495427http://purl.uniprot.org/core/author"Wang J."xsd:string
http://purl.uniprot.org/citations/37495427http://purl.uniprot.org/core/author"Zhang R."xsd:string
http://purl.uniprot.org/citations/37495427http://purl.uniprot.org/core/date"2024"xsd:gYear
http://purl.uniprot.org/citations/37495427http://purl.uniprot.org/core/name"Dig Liver Dis"xsd:string
http://purl.uniprot.org/citations/37495427http://purl.uniprot.org/core/pages"281-290"xsd:string
http://purl.uniprot.org/citations/37495427http://purl.uniprot.org/core/title"Integrated analysis and validation of TRIM23/p53 signaling pathway in hepatic stellate cells ferroptosis and liver fibrosis."xsd:string
http://purl.uniprot.org/citations/37495427http://purl.uniprot.org/core/volume"56"xsd:string
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http://purl.uniprot.org/citations/37495427http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/37495427
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