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

IF 2.8 3区医学 Q3 ENDOCRINOLOGY & METABOLISM

Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy Pub Date : 2025-04-15 eCollection Date: 2025-01-01 DOI:10.2147/DMSO.S486377

Wen Xia, Li Xiao, Huan Cheng, Yuwei Feng

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引用次数: 0

Abstract

Background: 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.

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TRIB3是脂肪性肝炎的枢纽基因，可加重肝细胞的脂质沉积和炎症。

背景：非酒精性脂肪性肝病（NAFLD），又称代谢功能障碍相关脂肪性肝病（MASLD），已成为世界范围内最常见的慢性肝病之一，约30%的成年人和70%~80%的肥胖和糖尿病患者患有NAFLD。目的：在棕榈酸和油酸（PAOA）诱导的NAFLD肝细胞模型中寻找一个潜在的中枢基因，并研究其功能。方法：从GEO-DataSets检索并下载GSE122660数据集，使用R软件对差异表达基因（differential expression genes, DEGs）进行分析。通过基因本体（GO）和京都基因与基因组百科全书（KEGG）途径富集分析，确定脂肪性肝炎中显著激活的信号通路。构建了蛋白-蛋白相互作用（PPI）网络，以鉴定deg中的枢纽基因。采用qRT-PCR、Western blotting、Oil Red O染色等方法研究paoa诱导肝细胞hub基因的功能。结果：在GSE122660数据集中共鉴定了255个deg，主要与炎症和脂质代谢相关途径相关。tribles pseudokinase 3 （TRIB3）是一个中心基因。我们发现TRIB3在cdhf诱导的NAFLD小鼠肝组织和肝细胞模型中上调。此外，TRIB3加重了paoa诱导的肝细胞脂质积累和炎症。结论：本研究确定TRIB3是脂肪性肝炎和体外脂质积累和炎症加重的枢纽基因。因此，靶向TRIB3可能是治疗NAFLD的潜在药理策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy Pharmacology, Toxicology and Pharmaceutics-Pharmacology

CiteScore

5.90

自引率

6.10%

发文量

431

审稿时长

16 weeks

期刊介绍： An international, peer-reviewed, open access, online journal. The journal is committed to the rapid publication of the latest laboratory and clinical findings in the fields of diabetes, metabolic syndrome and obesity research. Original research, review, case reports, hypothesis formation, expert opinion and commentaries are all considered for publication.