Integrative analysis of renal microRNA and mRNA to identify hub genes and pivotal pathways associated with cyclosporine-induced acute kidney injury in mice.

Qiaoling Yang, Xunjiang Wang, Hongjing Li, Xuedong Yin, Hongxia Liu, Wenjuan Hu, Ying Qing, Lili Ding, Li Yang, Zhiling Li, Huajun Sun
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Abstract

Cyclosporine (CsA) is an immunosuppressive agent that often causes acute kidney injury (AKI) in children. The specific mechanisms underlying CsA-induced AKI are currently unknown. This study used an integrated network analysis of microRNA (miRNA) and mRNA expression profiles, biochemical and pathological analyses to further investigate these potential mechanisms of CsA-induced AKI. Small RNA sequence analysis identified 25 differentially expressed miRNAs, RNA sequencing analysis identified 4,109 differentially expressed mRNAs. We obtained a total of 4,367 target genes from the 25 differentially expressed miRNAs based on three algorithms, including the Mirdb, Mirtarbase, and TargetScan. 971 target genes overlapped between the 4,367 target genes and 4,109 differentially expressed mRNAs were identified for further bioinformatics analysis. Finally, 30 hub genes and two main modules were recognized. Functional enrichment analysis of 30 hub genes indicated that inflammation and epithelial-mesenchymal transition (EMT) related genes were mainly concentrated together. Pathway analysis revealed that the PI3K-Akt signaling pathway plays an integral role in CsA-induced AKI. Network analysis identified 3 important miRNAs, mmu-miR-17b-5p, mmu-miR-19b-3p, and mmu-mir-423-5p that may further promote the development of inflammatory responses and EMT by mediating a complex network of factors. Our research provides a clearer understanding the molecular mechanism of this specific drug-induced AKI by CsA use, which is useful for discovering potential targets for gene therapies, and drug development in CsA-induced AKI.

肾脏microRNA和mRNA的整合分析,以确定环孢素诱导的小鼠急性肾损伤相关的枢纽基因和关键途径。
环孢素是一种免疫抑制剂,常引起儿童急性肾损伤(AKI)。csa诱发AKI的具体机制目前尚不清楚。本研究采用microRNA (miRNA)和mRNA表达谱的综合网络分析,生化和病理分析,进一步探讨csa诱导AKI的这些潜在机制。小RNA序列分析鉴定出25个差异表达的miRNAs, RNA测序分析鉴定出4109个差异表达的mrna。基于Mirdb、Mirtarbase和TargetScan三种算法,我们从25个差异表达的mirna中获得了总共4367个靶基因。在4367个靶基因和4109个差异表达mrna之间鉴定了971个重叠的靶基因,用于进一步的生物信息学分析。最终识别出30个枢纽基因和2个主要模块。30个hub基因的功能富集分析表明,炎症和上皮间质转化(epithelial-mesenchymal transition, EMT)相关基因主要集中在一起。通路分析显示,PI3K-Akt信号通路在csa诱导的AKI中起着不可或缺的作用。网络分析确定了3个重要的mirna, mmu-miR-17b-5p, mmu-miR-19b-3p和mmu-mir-423-5p,它们可能通过介导一个复杂的因素网络进一步促进炎症反应和EMT的发展。我们的研究为CsA使用这种特异性药物诱导AKI的分子机制提供了更清晰的认识,这有助于发现CsA诱导AKI的潜在基因治疗靶点和药物开发。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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