Janosevic Danielle, De Luca Thomas, Ferreira Ricardo Melo, Gisch Debora L, Hato Takashi, Luo Jinghui, Yang Yingbao, Hodgin Jeffrey B, Dagher Pierre C, Eadon Michael T
bioRxiv. 2023 Sep 12:2023.09.11.557054. doi: 10.1101/2023.09.11.557054.
Acute kidney injury (AKI) is an important contributor to the development of chronic kidney disease (CKD). There is a need to understand molecular mediators that drive either recovery or progression to CKD. In particular, the role of miRNA and its regulatory role in AKI is poorly understood. We performed miRNA and mRNA sequencing on biobanked human kidney tissues obtained in the routine clinical care of patients with the diagnoses of AKI and minimal change disease (MCD), in addition to nephrectomized (Ref) tissue from individuals without known kidney disease. Transcriptomic analysis of mRNA revealed that Ref tissues exhibited a similar injury signature to AKI, not identified in MCD samples. The transcriptomic signature of human AKI was enriched with genes in pathways involved in cell adhesion and epithelial-to-mesenchymal transition (e.g., ). miRNA DE analysis revealed upregulation of miRNA associated with immune cell recruitment and inflammation (e.g., miR-146a, miR-155, miR-142, miR-122). These miRNA (i.e., miR-122, miR-146) are also associated with downregulation of mRNA such as and , respectively. These findings suggest integrated interactions between miRNAs and target mRNAs in AKI-related processes such as inflammation, immune cell activation and epithelial-to-mesenchymal transition. These data contribute several novel findings when describing the epigenetic regulation of AKI by miRNA, and also underscores the importance of utilizing an appropriate reference control tissue to understand canonical pathway alterations in AKI.
急性肾损伤（AKI）是慢性肾脏病（CKD）发生发展的重要因素。有必要了解驱动肾脏恢复或进展为CKD的分子介质。特别是，miRNA在AKI中的作用及其调控机制尚不清楚。我们对在临床常规护理中获取的生物样本库中的人类肾脏组织进行了miRNA和mRNA测序，这些样本来自诊断为AKI和微小病变肾病（MCD）的患者，以及来自无已知肾脏疾病个体的肾切除（Ref）组织。对mRNA的转录组分析显示，Ref组织呈现出与AKI相似的损伤特征，而MCD样本中未发现这种特征。人类AKI的转录组特征富含参与细胞黏附及上皮-间质转化途径的基因（例如 ）。miRNA差异表达分析显示，与免疫细胞募集和炎症相关的miRNA上调（例如miR-146a、miR-155、miR-142、miR-122）。这些miRNA（即miR-122、miR-146）也分别与诸如 和 等mRNA的下调相关。这些发现表明，在AKI相关过程（如炎症、免疫细胞激活和上皮-间质转化）中，miRNA与靶mRNA之间存在整合相互作用。这些数据在描述miRNA对AKI的表观遗传调控时提供了一些新发现，也强调了利用合适的对照组织来理解AKI中经典信号通路改变的重要性。
