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Updated: Jul 1, 2025
Comparative Proteomic Analysis of Whole Kidney, Medulla, and Cortical Tubules in Diabetic Pathogenesis of Kidney Injury in Mice
Published on: May 2, 2025
Integrative transcriptomic and proteomic profile revealed inhibition of oxidative phosphorylation and peroxisomes
Cheng Wang1, Zhuo Pan2, Linxiao Sun3
1Department of Laboratory, Guizhou Provincial People's Hospital, Guiyang, Guizhou 550002, PR China.
Abstract:
Effective therapies of chronic kidney disease (CKD) are lacking due to the unclear molecular pathogenesis. Previous single omics-studies have described potential molecular regulation mechanism of CKD only at the level of transcription or translation. Therefore, this study generated an integrated transcriptomic and proteomic profile to provide deep insights into the continuous transcription-translation process during CKD. The comprehensive datasets identified 14,948 transcripts and 6423 proteins, 233 up-regulated and 364 down-regulated common differentially expressed genes of transcriptome and proteome were selected to further combined bioinformatics analysis. The obtained results revealed reactive oxygen species (ROS) metabolism and antioxidant system due to imbalance of mitochondria and peroxisomes were significantly repressed in CKD. Overall, this study presents a valuable multi-omics analysis that sheds light on the molecular mechanisms underlying CKD. SIGNIFICANCE: Chronic kidney disease (CKD) is a progressive and irreversible condition that results in abnormal kidney function and structure, and is ranked 18th among the leading causes of death globally, leading to a significant societal burden. Hence, there is an urgent need for research to detect new, sensitive, and specific biomarkers. Omics-based studies offer great potential to identify underlying disease mechanisms, aid in clinical diagnosis, and develop novel treatment strategies for CKD. Previous studies have mainly focused on the regulation of gene expression or protein synthesis in CKD, thereby compelling us to conduct a meticulous analysis of transcriptomic and proteomic data from the UUO mouse model. Here, we have performed a unified analysis of CKD model by integrating transcriptomes and protein suites for the first time. Our study contributes to a deeper understanding of the pathogenesis of CKD and provides a basis for subsequent disease management and drug development.
Insights
This study integrates transcriptomic and proteomic data to uncover chronic kidney disease (CKD) mechanisms. We found repressed reactive oxygen species (ROS) metabolism and antioxidant systems, offering new insights for CKD therapies.
Area of Science:
- Nephrology
- Molecular Biology
- Genomics and Proteomics
Background:
- Chronic kidney disease (CKD) lacks effective therapies due to unclear molecular pathogenesis.
- Previous single-omics studies provided incomplete insights into CKD molecular regulation.
- There is an urgent need for novel biomarkers and therapeutic strategies for CKD.
Purpose of the Study:
- To perform an integrated transcriptomic and proteomic analysis of CKD.
- To gain deeper insights into the continuous transcription-translation process in CKD.
- To identify molecular mechanisms underlying CKD pathogenesis.
Main Methods:
- Generated integrated transcriptomic and proteomic profiles from a UUO mouse model.
- Identified 14,948 transcripts and 6423 proteins.
- Performed combined bioinformatics analysis on common differentially expressed genes.
Main Results:
- Revealed significantly repressed reactive oxygen species (ROS) metabolism in CKD.
- Identified an imbalanced antioxidant system involving mitochondria and peroxisomes.
- Selected 233 up-regulated and 364 down-regulated common differentially expressed genes.
Conclusions:
- This multi-omics analysis sheds light on CKD molecular mechanisms.
- The findings provide a basis for understanding CKD pathogenesis.
- This study supports the development of future CKD management and drug discovery.
