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TRIB3 Is a Hub Gene in Steatohepatitis and Aggravates Lipid Deposition and Inflammation in Hepatocytes

Year: 2025
Type: article
Abstract: Wen Xia,1,* Li Xiao,1,* Huan Cheng,1 Yuwei Feng2 1Department of Cardiovascular Medicine, Wuhan No.1 Hospital, Wuhan, Hubei, People’s Republic of China; 2Department of Hepatology with Integrated Traditional Chinese and Western Medicine, Hubei No.3 People’s Hospital of Jianghan University, Wuhan, Hubei, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yuwei Feng, Department of Hepatology with Integrated Traditional Chinese and Western Medicine, Hubei No.3 People’s Hospital of Jianghan University, #26 Zhongshan Avenue, Wuhan, 430022, People’s Republic of China, Tel +86-27-85332356, Email [email protected]: Non-alcoholic fatty liver disease (NAFLD), also known as Metabolic dysfunction–associated fatty liver disease (MASLD), has become one of the most common chronic liver diseases worldwide, approximately 30% of adults and 70%~80% of patients with obesity and diabetes suffer from NAFLD.Objective: We attempted to find a potential hub gene in NAFLD hepatocyte cell model induced by palmitic acid and oil acid (PAOA), and investigated the function of the hub–gene.Methods: We searched and downloaded the GSE122660 dataset from GEO-DataSets, and differentially expressed genes (DEGs) were analyzed using R software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to identify the significantly activated signaling pathways in steatohepatitis. A protein-protein interaction (PPI) network was constructed to identify hub genes among the DEGs. qRT–PCR, Western blotting, and Oil Red O staining were used to explore the function of hub genes in PAOA–induced hepatocytes in vitro.Results: A total of 255 DEGs were identified in the GSE122660 dataset and were primarily associated with inflammation-and lipid metabolism-related pathways. The tribbles pseudokinase 3 (TRIB3) was highlighted as a hub gene. We found that TRIB3 was upregulated in CDHFDinduced NAFLD mouse liver tissue and hepatocyte cell models. Furthermore, TRIB3 aggravated PAOA-induced lipid accumulation and inflammation in hepatocytes in vitro.Conclusion: The present study identified TRIB3 as a hub gene for steatohepatitis and aggravated lipid accumulation and inflammation in vitro. Therefore, targeting TRIB3 could be a potential pharmacological strategy for NAFLD treatment.Keywords: non-alcoholic fatty liver disease, steatohepatitis, hub gene, TRIB3, lipid accumulation, inflammation
Authors: Xia W, Xiao L, Cheng H, Feng Y
Language: English
Subfield: Epidemiology
Field: Medicine
Open Access status: green
OpenAlex ID: W7015890963
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