Wang Binqi, He Wenfang, Xie Zhixuan, Zhang Jinshi, Ren Yan, He Qiang, Jin Juan
The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310000, People's Republic of China.
Urology & Nephrology Center, Department of Nephrology, Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, People's Republic of China.
Sci Rep. 2024 Dec 30;14(1):31754. doi: 10.1038/s41598-024-81944-4.
Diabetes nephropathy (DN) is a prevalent and severe microvascular diabetic complication. Despite the recent developments in germacrone-based therapies for DN, the underlying mechanisms of germacrone in DN remain poorly understood. This study used comprehensive bioinformatics analysis to identify critical microRNAs (miRNAs) and the potential underlying pathways related to germacrone activities. Additionally, we established a DN mice model, which was treated with germacrone, to investigate how it altered the miRNA transcriptome in mice kidneys. RNA sequencing was also performed on the DN mice model with and without germacrone pre-treatment. Based on our results, we found 23 miRNAs were differentially expressed in the DN group compared to the controls, and a total of 14 miRNAs were differentially expressed between the DN group and the germacrone-treated group. In addition, we identified three miRNAs (mmu-miR-542-5p, mmu-miR-149-5p and mmu-miR-196a-2-3p) that were upregulated with the DN group and downregulated in the germacrone-treated group. Bioinformatics analysis suggested that autophagy and apoptosis were related to the pathogenesis of DN and germacrone treatment. Subsequently, the expression level of mmu-miR-542-5p, mmu-miR-149-5p and mmu-miR-196a-2-3p were validated in a validation dataset. Altogether, these findings add important knowledge on the pathogenesis of DN and the impacts of germacrone.
糖尿病肾病（DN）是一种常见且严重的糖尿病微血管并发症。尽管近年来基于莪术酮的DN治疗取得了进展，但莪术酮在DN中的潜在机制仍知之甚少。本研究采用综合生物信息学分析来识别关键的微小RNA（miRNA）以及与莪术酮作用相关的潜在途径。此外，我们建立了一个用莪术酮治疗的DN小鼠模型，以研究其如何改变小鼠肾脏中的miRNA转录组。还对有或没有莪术酮预处理的DN小鼠模型进行了RNA测序。根据我们的结果，我们发现与对照组相比，DN组中有23种miRNA差异表达，DN组和莪术酮治疗组之间共有14种miRNA差异表达。此外，我们鉴定出三种miRNA（mmu-miR-542-5p、mmu-miR-149-5p和mmu-miR-196a-2-3p）在DN组中上调，而在莪术酮治疗组中下调。生物信息学分析表明，自噬和凋亡与DN的发病机制及莪术酮治疗有关。随后，在一个验证数据集中验证了mmu-miR-542-5p、mmu-miR-149-5p和mmu-miR-196a-2-3p的表达水平。总之，这些发现为DN的发病机制及莪术酮的影响增添了重要知识。
