摘要
[目的]初步筛选镉暴露早期肾脏组织差异表达的微小RNA(miRNA),并探讨差异表达miR-21的靶基因主要参与的GO富集与KEGG通路。[方法]24只SPF级SD雄性大鼠随机分为4组,分别为对照组和低、中、高镉暴露组。大鼠背部皮下注射0、0.5、1.0和2.0 mg/kg氯化镉溶液,每周5 d,持续2周。基因芯片筛选差异表达的miRNA,实时定量PCR验证差异表达的miR-21,并对差异表达的miR-21进行生物信息学分析;酶联免疫吸附实验检测肾功能指标。[结果]与对照组相比,2.0 mg/kg镉暴露导致大鼠出现了肾损伤(P<0.05),且可以增强miR-21在肾脏组织的表达水平(P<0.05)。miR-21靶基因主要集中于DNA调节转录、氨基酸磷酸化、氧化应激等生物学过程及与蛋白结合、转录因子结合等分子功能上,存在于细胞核、细胞膜、细胞质、线粒体、内质网等细胞组分中,主要参与MAPK信号通路、转化生长因子-β信号通路。[结论]miR-21在镉暴露所致大鼠肾损伤中表达上调,并可能参与多条信号通路的调控。
[ Objective ] To explore the early differential expression of microRNA （miRNA） of rat＇s injured kidney induced by cadmium exposure, and to predict the target genes which mainly participate in the Gene Ontology （GO） enrichment and Kyoto Encyclopedia of Gene and Genomes （KEGG） pathway. [ Methods ] Twenty-four SPF-grade SD male rats were randomly divided into four groups and given subcutaneous injection of 0, 0.5, 1.0, and 2.0mg/kg CdCl2, respectively, 5 days per week for 2 weeks. Gene chip technology and real time polymerase chain reaction were employed to explore and verify the differential expression of miRNA. The miR-21 with differential expression was subjected to bioinformatics analysis. Enzyme-linked immunosorbent assay was used to detect the indices of renal function. [ Results ] Compared with the control group, renal damage were found in the 2.0mg/kg Cd-exposed group （P〈0.05） and the expression of miR-21 was enhanced （P〈0.05）. miR-21 target genes were mainly enriched in biological processes （DNA regulated transcription, amino acid phosphorylation, and oxidative stress）, molecular factions （protein binding and transcription factors binding）, and cell components such as cell nucleus, membrane, cytoplasm, mitochondria, and endoplasmic reticulum. They also involved in MAPK and transforming growth factor-β signaling pathways. [ Conclusion ] miR-21 is up-regulated in the injured rat renal tissues induced by cadmium exposure and may play an important role through multiple signal transduction pathways.
出处
《环境与职业医学》
CAS
CSCD
北大核心
2016年第2期113-118,共6页
Journal of Environmental and Occupational Medicine
基金
国家自然科学基金(编号:81273040)
山西省自然科学基金(编号:2012011039-7)
