Weng Chun-Yue, Zhu Mo-Han, Dai Ke-Lei, Mi Zhe-Yan, Wang Yuan-Shan, Liu Zhi-Qiang, Zheng Yu-Guo
The National and Local Joint Engineering Research Center for Biomanufacturing of Chiral Chemicals, Zhejiang University of Technology, Hangzhou, China.
Key Laboratory of Bioorganic Synthesis of Zhejiang Province, College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou, China.
Front Bioeng Biotechnol. 2021 May 21;9:659700. doi: 10.3389/fbioe.2021.659700. eCollection 2021.
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 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.
阿卡波糖是一种治疗2型糖尿病(T2DM)的有效抗糖尿病药物,2型糖尿病是一种由胰岛素抵抗引起的慢性退行性代谢疾病。许多研究已证实阿卡波糖对T2DM患者血糖控制的有益作用。然而,阿卡波糖对患者肾脏的影响尚未完全阐明。在本研究中,我们基于对GSE59913微阵列数据集的深入分析,详细报告了阿卡波糖处理的肾脏中的基因表达级联变化、通路和模块富集以及相互关系网络。通过比较分析初步筛选出阿卡波糖处理的大鼠肾脏中显著差异表达的基因(DEGs)。进一步确定了基因本体论(GO)和京都基因与基因组百科全书(KEGG)分析的富集通路。通过STRING数据库挖掘实现了对DEGs的蛋白质-蛋白质相互作用(PPI)分析。进一步研究富集通路的通路相互关系和枢纽基因,以揭示阿卡波糖的关键生物学效应。结果显示,在阿卡波糖处理的大鼠肾脏中,有44个基因显著上调,86个基因显著下调(总共130个显著差异基因)。阿卡波糖显著改善了脂质代谢途径,慢性肾脏病(CKD)患者的身体状况可能通过卵磷脂胆固醇酰基转移酶(LCAT)提高高密度脂蛋白(HDL)水平而得到改善。这些发现表明,阿卡波糖可能是CKD患者的理想药物,因为它不仅可以保护肾脏,还可能缓解CKD引起的并发症。