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Updated: Jan 3, 2026
Mouse Model of Metabolic Dysfunction-Associated Steatotic Liver Disease with Fibrosis
Published on: July 18, 2025
RNA-Seq analysis of the pathogenesis of STZ-induced male diabetic mouse liver
Qi Ge1, Fan Feng2, Lanlan Liu3
1School of the Environment and Safety Engineering, Jiangsu University, Zhenjiang, Jiangsu 212013, PR China; Institute of Life Sciences, Jiangsu University, Zhenjiang, Jiangsu 212013, PR China.
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.
Insights
This study identified key genes and pathways involved in diabetes pathogenesis, focusing on liver metabolism and immune responses. Findings suggest potential new therapeutic targets for diabetes treatment.
Area of Science:
- Biochemistry
- Genomics
- Immunology
Background:
- Diabetes mellitus (DM) is a chronic condition marked by hyperglycemia.
- The liver plays a crucial role in glucose metabolism, but key protein changes in DM pathogenesis remain unclear.
Purpose of the Study:
- To investigate transcriptional and protein expression differences in the liver of a diabetic mouse model.
- To identify key genes and pathways implicated in the pathogenesis of diabetes.
Main Methods:
- Induced diabetes in mice using streptozotocin (STZ).
- Performed RNA-sequencing (RNA-Seq) to analyze liver gene expression.
- Validated differentially expressed genes using quantitative real-time PCR (qRT-PCR) and Western blotting.
- Constructed protein-protein interaction (PPI) networks.
Main Results:
- Identified 370 up-regulated and 281 down-regulated genes in diabetic mouse livers.
- Gene Ontology (GO) and KEGG pathway analyses indicated involvement in immunity, enzyme activity, metabolism, and steroid synthesis.
- Fifteen core differential proteins were identified, including Cyp51a1, Acsl4, and Sqle, implicated in diabetes pathogenesis.
- Discrepancies in gene expression validation suggested potential post-transcriptional regulation by Sqle.
Conclusions:
- Diabetes pathogenesis may involve steroid biosynthesis, metabolic processes, and immune responses.
- The identified pathways and proteins represent potential targets for novel diabetes prevention and treatment strategies.
