基于生物信息学和实验验证鉴定 Timm13 蛋白作为潜在的肝纤维化介导线粒体内膜转位酶。
Identification of Timm13 protein translocase of the mitochondrial inner membrane as a potential mediator of liver fibrosis based on bioinformatics and experimental verification.
机构信息
Department of Gastroenterology, The First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning, 530021, Guangxi, China.
Department of Gastroenterology, The Third Affiliated Hospital of Guangxi Medical University, Nanning, 530000, Guangxi, China.
出版信息
J Transl Med. 2023 Mar 10;21(1):188. doi: 10.1186/s12967-023-04037-2.
OBJECTIVE
To explore the association between translocase of the inner mitochondrial membrane 13 (Timm13) and liver fibrosis.
METHODS
Gene expression profiles of GSE167033 were collected from Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) between liver disease and normal samples were analyzed using GEO2R. Gene Ontology and Enrichment function were performed, a protein-protein interaction (PPI) network was constructed via the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING), and the hub genes of the PPI network were calculated by MCODE plug-in in Cytoscape. We validated the transcriptional and post-transcriptional expression levels of the top correlated genes using fibrotic animal and cell models. A cell transfection experiment was conducted to silence Timm13 and detect the expression of fibrosis genes and apoptosis genes.
RESULTS
21,722 genes were analyzed and 178 DEGs were identified by GEO2R analysis. The top 200 DEGs were selected and analyzed in STRING for PPI network analysis. Timm13 was one of the hub genes via the PPI network. We found that the mRNA levels of Timm13 in fibrotic liver tissue decreased (P < 0.05), and the mRNA and protein levels of Timm13 also decreased when hepatocytes were stimulated with transforming growth factor-β1. Silencing Timm13 significantly reduced the expression of profibrogenic genes and apoptosis related genes.
CONCLUSIONS
The results showed that Timm13 is closely related to liver fibrosis and silencing Timm13 significantly reduced the expression of profibrogenic genes and apoptosis related genes, which will provide novel ideas and targets for the clinical diagnosis and treatment of liver fibrosis.
目的
探讨内膜转位酶 13（Timm13）与肝纤维化的关系。
方法
从基因表达综合数据库（GEO）中收集 GSE167033 的基因表达谱。使用 GEO2R 分析肝病和正常样本之间的差异表达基因（DEGs）。进行基因本体论和富集功能分析，通过 Search Tool for the Retrieval of Interacting Genes/Proteins（STRING）构建蛋白质-蛋白质相互作用（PPI）网络，并通过 Cytoscape 中的 MCODE 插件计算 PPI 网络的枢纽基因。我们使用纤维化动物和细胞模型验证了 top 相关基因的转录和转录后表达水平。通过细胞转染实验沉默 Timm13 并检测纤维化基因和凋亡基因的表达。
结果
通过 GEO2R 分析，分析了 21722 个基因，鉴定了 178 个 DEGs。选择前 200 个 DEGs 进行 STRING 的 PPI 网络分析。通过 PPI 网络，Timm13 是其中一个枢纽基因。我们发现纤维化肝组织中 Timm13 的 mRNA 水平降低（P<0.05），当肝细胞受到转化生长因子-β1 刺激时，Timm13 的 mRNA 和蛋白水平也降低。沉默 Timm13 显著降低了促纤维化基因和凋亡相关基因的表达。
结论
结果表明，Timm13 与肝纤维化密切相关，沉默 Timm13 显著降低了促纤维化基因和凋亡相关基因的表达，这将为肝纤维化的临床诊断和治疗提供新的思路和靶点。
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