RNA-Seq analysis of the pathogenesis of STZ-induced male diabetic mouse liver

Qi Ge; Fan Feng; Lanlan Liu; Liang Chen; Peng Lv; Shangshang Ma; Keping Chen; Qin Yao

doi:10.1016/j.jdiacomp.2019.107444

RNA-Seq analysis of the pathogenesis of STZ-induced male diabetic mouse liver

J Diabetes Complications. 2020 Feb;34(2):107444. doi: 10.1016/j.jdiacomp.2019.107444. Epub 2019 Sep 13.

Authors

Qi Ge¹, Fan Feng², Lanlan Liu³, Liang Chen³, Peng Lv³, Shangshang Ma³, Keping Chen⁴, Qin Yao⁵

Affiliations

¹ School of the Environment and Safety Engineering, Jiangsu University, Zhenjiang, Jiangsu 212013, PR China; Institute of Life Sciences, Jiangsu University, Zhenjiang, Jiangsu 212013, PR China.
² The Fourth Affiliated Hospital of Jiangsu University, 20# Zhengdong Road, Zhenjiang, Jiangsu 212001, PR China.
³ Institute of Life Sciences, Jiangsu University, Zhenjiang, Jiangsu 212013, PR China.
⁴ Institute of Life Sciences, Jiangsu University, Zhenjiang, Jiangsu 212013, PR China. Electronic address: kpchen@ujs.edu.cn.
⁵ School of the Environment and Safety Engineering, Jiangsu University, Zhenjiang, Jiangsu 212013, PR China; Institute of Life Sciences, Jiangsu University, Zhenjiang, Jiangsu 212013, PR China. Electronic address: yaoqin@ujs.edu.cn.

PMID: 31757765
DOI: 10.1016/j.jdiacomp.2019.107444

Abstract

Objective: Diabetes mellitus (DM) is a chronic disease characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both. The liver is a key organ involved in glucose metabolism, and the major target proteins' changes in the pathogenesis are still unknown.

Methods: A diabetic mouse model was induced by intraperitoneal injection of streptozotocin (STZ) solution and the RNA-Seq analysis was used to evaluate the transcription differences in the livers of diabetic mice of this study. And then, the differentially expressed genes were validated between a normal mouse group (n = 6) and a diabetic mouse group (n = 6) using quantitative real-time PCR (qRT-PCR) and Western blotting analysis. In addition, we also constructed protein-protein interacting (PPI) networks of up-regulated and down-regulated genes.

Results: Transcriptome sequencing analysis revealed 370 up-regulated differentially expressed genes and 281 down-regulated differentially expressed genes in the diabetes model. The gene ontology (GO) analysis and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis results showed that the differentially expressed genes were mainly involved in immunity, enzyme activity, metabolism, and steroid synthesis. PPI analysis results indicated that the main 15 core differential proteins (Cyp51a1, Acsl4, Ugt1a1, Stat1, Gsta2, Cbr1, Aldh1a1, Fasn, Ces1, Camk2b, Tap1, Egr1, Sqle, Lpin1, Fabp5) were involved in the pathogenesis of diabetes. The qRT-PCR results showed that expression changes of four genes (Acsl4, Stat1, Gsta2, Fabp5) were in different directions from those of RNA-Seq. Western blotting results indicated that Sqle expression change at the protein level was in opposition direction from qRT-PCR, and we speculated that Sqle may be involved in the post-transcriptional modification process.

Conclusions: Our data speculated that the pathogenesis of diabetes may be mediated mainly through steroid biosynthesis, metabolic processes, and immune responses. Further researches on these pathways may provide new targets for the prevention and treatment of diabetes.

Keywords: Diabetes mellitus; Differentially expressed genes; Insulin resistance; Liver; RNA-Seq; Steroid biosynthesis.

Publication types

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

MeSH terms

Animals
Diabetes Mellitus, Experimental / immunology
Diabetes Mellitus, Experimental / metabolism
Diabetes Mellitus, Experimental / physiopathology*
Disease Models, Animal
Liver / immunology
Liver / metabolism
Liver Diseases* / etiology
Liver Diseases* / genetics
Liver Diseases* / immunology
Liver Diseases* / metabolism
Male
Mice
RNA-Seq*
Streptozocin
Transcriptome

Substances

Streptozocin