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. 2021 May 21:9:659700.
doi: 10.3389/fbioe.2021.659700. eCollection 2021.

Gene Cascade Shift and Pathway Enrichment in Rat Kidney Induced by Acarbose Through Comparative Analysis

Chun-Yue Weng  1   2   3 , Mo-Han Zhu  1   2   3 , Ke-Lei Dai  1   2   3 , Zhe-Yan Mi  1   2   3 , Yuan-Shan Wang  1   2   3 , Zhi-Qiang Liu  1   2   3 , Yu-Guo Zheng  1   2   3
Affiliations

Gene Cascade Shift and Pathway Enrichment in Rat Kidney Induced by Acarbose Through Comparative Analysis

Chun-Yue Weng et al. Front Bioeng Biotechnol. .

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.

Keywords: Rattus norvegicus; acarbose; comparative analysis; kidney; lipid metabolism.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Volcano plot and heatmap of differential genes between Acarbose and Water. (A) All 6084 differential genes were utilized for volcano plot. Red: significantly up-regulated in Acarbose; blue: significantly down-regulated in Acarbose; yellow: no significant change. (B) The top 150 most significantly up-regulated and 150 most significantly down-regulated genes were utilized for heatmap presentation. Red, up-regulated genes in Acarbose; blue, down-regulated genes in Acarbose. Samples showed distinct gene expression patterns between the two groups, but comparable expression patterns within a group.
FIGURE 2
FIGURE 2
The protein-protein interaction (PPI) network of differentially expressed genes (DEGs) between Acarbose and Water. The 130 significant DGEs were employed for PPI network construction. Each node represented a protein, and each connection represented an interaction. Module A and B were the most significantly enriched functional protein modules. Module A: the hormone receptor module; Module B: the lipoprotein module. The cutoff for module filtration is: MCODE score > 3, and nodes > 3.
FIGURE 3
FIGURE 3
Interrelation analyses between differential pathways between Acarbose and Water. The interrelation of biological process (GO), cellular component (GO), molecular function (GO), and KEGG for the differentially expressed genes (DEGs) between Acarbose and Water was analyzed using the ClueGo plugin in Cytoscape. Each node corresponded to a term, the size of the node corresponded to the universality of the term in the enriched genes, and the connection between the nodes showed the correlations between different terms. Modules in different colors represented different functions. The selection threshold for terms/pathways is p < 0.05.
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