在啮齿动物肾病模型中鉴定被纳仁曼杜拉靶向的关键微小RNA
Identifying Key MicroRNAs Targeted by Narenmandula in a Rodent Nephropathy Model.
作者信息
Wang Xiulan, Chang Chun, Jin Wenjie, Arun Arun, Sudunabuqi Sudunabuqi, Aodaofu Aodaofu, Liu Xiaowei, Wu Fengjiao, Chen Hongmei
机构信息
Mongolia Medical Department of Inner Mongolia University for the Nationalities, Inner Mongolia Autonomous of China, Tongliao 028000, China.
Affiliated Hospital of Inner Mongolia University for the Nationalities, Inner Mongolia Autonomous of China, Tongliao 028000, China.
出版信息
Evid Based Complement Alternat Med. 2020 Nov 24;2020:9196379. doi: 10.1155/2020/9196379. eCollection 2020.
BACKGROUND
Untreated nephropathy can progress to renal failure. The traditional Mongolian remedy Narenmandula regulates the kidney "yang." This study aimed to identify key microRNAs (miRNAs) targeted by Narenmandula in a rat model of nephropathy.
METHODS
Fifteen rats exhibiting normal renal function were randomized to three study arms. Nephropathy was induced in = 10 rats using doxorubicin hydrochloride, followed by either Narenmandula treatment (treatment group) or no treatment (control group). In = 5 rats, no doxorubicin was given and renal function remained unchanged (healthy group). Microarray analysis identified miRNAs which were differentially expressed (DE-miRNAs) between groups. Target genes of DE-miRNAs were predicted using miRWalk version 2.0, followed by enrichment analysis using DAVID, and construction of the miRNA coregulatory network using Cytoscape.
RESULTS
Nephropathy was successfully induced, with doxorubicin resulting in differential expression of 3645 miRNAs (1324 upregulated and 2321 downregulated). Narenmandula treatment induced differential expression of a total of 159 miRNAs (102 upregulated and 57 downregulated). Upregulated DE-miRNAs (e.g., miR-497-5p, miR-195-5p, miR-181a-5p, miR-181c-5p, and miR-30e-5p) and downregulated DE-miRNAs (e.g., miR-330-3p and miR-214-3p) regulated a high number of target genes. Moreover, the miRNA pairs (e.g., miR-195-5p-miR-497-5p, miR-181a-5p-miR-181c-5p, and miR-30e-5p-miR-30a-5p) coregulated a high number of genes. Enrichment analysis indicated functional synergy between miR-30e-5p-miR-30a-3p, miR-34a-5p-miR-30e-5p, miR-30e-5p-miR-195-3p, and miR-30a-3p-miR-195-3p pairs.
CONCLUSION
Narenmandula may modulate doxorubicin-induced nephropathy via targeting miR-497-5p, miR-195-5p, miR-181a-5p, miR-181c-5p, miR-30e-5p, miR-330-3p, miR-214-3p, miR-34a-5p, miR-30a-3p, and miR-30a-5p.
背景
未经治疗的肾病可进展为肾衰竭。传统蒙古疗法那仁满都拉可调节肾阳。本研究旨在鉴定那仁满都拉在肾病大鼠模型中靶向的关键微小RNA（miRNA）。
方法
将15只肾功能正常的大鼠随机分为三个研究组。对10只大鼠用盐酸阿霉素诱导肾病，随后分别给予那仁满都拉治疗（治疗组）或不治疗（对照组）。对5只大鼠不给予阿霉素，肾功能保持不变（健康组）。通过微阵列分析鉴定组间差异表达的miRNA（DE-miRNA）。使用miRWalk 2.0版本预测DE-miRNA的靶基因，随后使用DAVID进行富集分析，并使用Cytoscape构建miRNA共调控网络。
结果
成功诱导出肾病，阿霉素导致3645个miRNA差异表达（1324个上调，2321个下调）。那仁满都拉治疗共诱导159个miRNA差异表达（102个上调，57个下调）。上调的DE-miRNA（如miR-497-5p、miR-195-5p、miR-181a-5p、miR-181c-5p和miR-30e-5p）和下调的DE-miRNA（如miR-330-3p和miR-214-3p）调控大量靶基因。此外，miRNA对（如miR-195-5p-miR-497-5p、miR-181a-5p-miR-181c-5p和miR-30e-5p-miR-30a-5p）共调控大量基因。富集分析表明miR-30e-5p-miR-30a-3p、miR-34a-5p-miR-30e-5p、miR-30e-5p-miR-195-3p和miR-30a-3p-miR-195-3p对之间存在功能协同作用。
结论
那仁满都拉可能通过靶向miR-497-5p、miR-195-5p、miR-181a-5p、miR-181c-5p、miR-30e-5p、miR-330-3p、miR-214-3p、miR-34a-5p、miR-30a-3p和miR-30a-5p来调节阿霉素诱导的肾病。
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