Identification of Timm13 protein translocase of the mitochondrial inner membrane as a potential mediator of liver fibrosis based on bioinformatics and experimental verification

Xiaomin Liao; Xianxian Ruan; Xianbin Wu; Zhejun Deng; Shanyu Qin; Haixing Jiang

doi:10.1186/s12967-023-04037-2

Identification of Timm13 protein translocase of the mitochondrial inner membrane as a potential mediator of liver fibrosis based on bioinformatics and experimental verification

J Transl Med. 2023 Mar 10;21(1):188. doi: 10.1186/s12967-023-04037-2.

Authors

Xiaomin Liao^#¹, Xianxian Ruan^#¹, Xianbin Wu², Zhejun Deng¹, Shanyu Qin³, Haixing Jiang⁴

Affiliations

¹ Department of Gastroenterology, The First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning, 530021, Guangxi, China.
² Department of Gastroenterology, The Third Affiliated Hospital of Guangxi Medical University, Nanning, 530000, Guangxi, China.
³ Department of Gastroenterology, The First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning, 530021, Guangxi, China. qinshanyu@gxmu.edu.cn.
⁴ Department of Gastroenterology, The First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning, 530021, Guangxi, China. jianghaixing@gxmu.edu.cn.

^# Contributed equally.

Abstract

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.

Keywords: Hepatocytes; Liver disease; Liver fibrosis; Timm13; Translocase of inner mitochondrial membrane.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Computational Biology / methods
Gene Expression Profiling*
Gene Regulatory Networks*
Liver Cirrhosis
Mitochondrial Membranes
RNA, Messenger / genetics

Substances

RNA, Messenger