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Gene Cascade Shift and Pathway Enrichment in Rat Kidney Induced by Acarbose Through Comparative Analysis
Chun-Yue Weng1,2,3, Mo-Han Zhu1,2,3, Ke-Lei Dai1,2,3
1The National and Local Joint Engineering Research Center for Biomanufacturing of Chiral Chemicals, Zhejiang University of Technology, Hangzhou, China.
Abstract:
Acarbose is an effective anti-diabetic drug to treat type 2 diabetes mellitus (T2DM), a chronic degenerative metabolic disease caused by insulin resistance. The beneficial effects of acarbose on blood sugar control in T2DM patients have been confirmed by many studies. However, the effect of acarbose on patient kidney has yet to be fully elucidated. In this study, we report in detail the gene expression cascade shift, pathway and module enrichment, and interrelation network in acarbose-treated Rattus norvegicus kidneys based on the in-depth analysis of the GSE59913 microarray dataset. The significantly differentially expressed genes (DEGs) in the kidneys of acarbose-treated rats were initially screened out by comparative analysis. The enriched pathways for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were further identified. The protein-protein interaction (PPI) analysis for DEGs was achieved through the STRING database mining. Pathway interrelation and hub genes for enriched pathways were further examined to uncover key biological effects of acarbose. Results revealed 44 significantly up-regulated genes and 86 significantly down-regulated genes (130 significant differential genes in total) in acarbose-treated rat kidneys. Lipid metabolism pathways were considerably improved by acarbose, and the physical conditions in chronic kidney disease (CKD) patients were improved possibly through the increase of the level of high-density lipoprotein (HDL) by lecithin-cholesterol acyl-transferase (LCAT). These findings suggested that acarbose may serve as an ideal drug for CKD patients, since it not only protects the kidney, but also may relieve the complications caused by CKD.
Insights
Acarbose treatment improves kidney function in rats by enhancing lipid metabolism and potentially increasing high-density lipoprotein (HDL) levels. This suggests acarbose may benefit patients with chronic kidney disease (CKD).
Area of Science:
- Nephrology
- Pharmacology
- Genomics
Background:
- Acarbose is an established treatment for type 2 diabetes mellitus (T2DM).
- Its effects on kidney health in T2DM patients remain incompletely understood.
- Understanding acarbose's renal impact is crucial for managing diabetic complications.
Purpose of the Study:
- To investigate the molecular mechanisms of acarbose's effects on rat kidneys.
- To analyze gene expression changes, pathway enrichment, and protein interactions in response to acarbose.
- To identify potential therapeutic benefits of acarbose for chronic kidney disease (CKD).
Main Methods:
- Analysis of the GSE59913 microarray dataset from acarbose-treated rats.
- Identification of significantly differentially expressed genes (DEGs) using comparative analysis.
- Enrichment analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways.
- Protein-protein interaction (PPI) network construction using the STRING database.
Main Results:
- Identified 130 significant DEGs in acarbose-treated rat kidneys (44 up-regulated, 86 down-regulated).
- Acarbose significantly improved lipid metabolism pathways.
- Potential mechanism involves increased lecithin-cholesterol acyl-transferase (LCAT) activity, raising high-density lipoprotein (HDL) levels.
Conclusions:
- Acarbose demonstrates a protective effect on the kidney in a rat model.
- The drug may improve CKD patient conditions by modulating lipid metabolism.
- Acarbose shows promise as a therapeutic agent for managing CKD and its complications.
