Cui Rui, Xu Jia, Chen Xiao, Zhu Wenliang
Department of Nephrology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
Department of Nephrology, Heilongjiang Province Hospital, Harbin, Heilongjiang, China.
PeerJ. 2016 Feb 25;4:e1729. doi: 10.7717/peerj.1729. eCollection 2016.
MicroRNAs (miRNAs) are negative regulators of gene expression and protein abundance. Current evidence shows an association of miRNAs with acute kidney injury (AKI) leading to substantially increased morbidity and mortality. Here, we investigated whether miRNAs are inductive regulators responsible for the pathological development of AKI. Microarray analysis was used to detect temporal changes in global miRNA expression within 48 h after AKI in mice. Results indicated that global miRNA expression gradually increased over 24 h from ischemia reperfusion injury after 24 h, and then decreased from 24 h to 48 h. A similar trend was observed for the index of tubulointerstitial injury and the level of serum creatinine, and there was a significant correlation between the level of total miRNA expression and the level of serum creatinine (p < 0.05). This expression-phenotype correlation was validated by quantitative reverse transcription PCR on individual miRNAs, including miR-18a, -134, -182, -210 and -214. Increased global miRNA expression may lead to widespread translational repression and reduced cellular activity. Furthermore, significant inflammatory cytokine release and peritubular capillary loss were observed, suggesting that the initiation of systematic destruction programs was due to AKI. Our findings provide new understanding of the dominant role of miRNAs in promoting the pathological development of AKI.
微小RNA（miRNA）是基因表达和蛋白质丰度的负调控因子。目前的证据表明，miRNA与急性肾损伤（AKI）相关，会导致发病率和死亡率大幅增加。在此，我们研究了miRNA是否为导致AKI病理发展的诱导性调控因子。采用微阵列分析检测小鼠AKI后48小时内整体miRNA表达的时间变化。结果表明，整体miRNA表达在缺血再灌注损伤后24小时内逐渐升高，之后从24小时到48小时逐渐降低。肾小管间质损伤指数和血清肌酐水平也呈现类似趋势，总miRNA表达水平与血清肌酐水平之间存在显著相关性（p < 0.05）。通过对包括miR-18a、-134、-182、-210和-214在内的单个miRNA进行定量逆转录PCR，验证了这种表达-表型相关性。整体miRNA表达增加可能导致广泛的翻译抑制和细胞活性降低。此外，观察到显著的炎性细胞因子释放和肾小管周围毛细血管丧失，提示系统性破坏程序的启动是由AKI所致。我们的研究结果为miRNA在促进AKI病理发展中的主导作用提供了新的认识。
