Janosevic Danielle, De Luca Thomas, Melo Ferreira Ricardo, Gisch Debora L, Cheng Ying-Hua, Hato Takashi, Luo Jinghui, Yang Yingbao, Hodgin Jeffrey B, Phillips Carrie L, Dagher Pierre C, Eadon Michael T
Division of Nephrology, Indiana University School of Medicine, Indianapolis, Indiana.
Division of Nephrology, Indiana University School of Medicine, Indianapolis, Indiana.
Am J Pathol. 2025 Jan;195(1):102-114. doi: 10.1016/j.ajpath.2024.08.013. Epub 2024 Sep 25.
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 recovery and progression to CKD. In particular, the regulatory role of miRNAs in AKI is poorly understood. Herein, miRNA and mRNA sequencing were performed on biobanked human kidney tissues obtained during the routine care of subjects with a diagnosis of AKI, minimal change disease, or on nephrectomy tissue with no known kidney disease. mRNA analysis revealed that nephrectomy tissues exhibited an injury signature similar to that of AKI which was not identified in minimal change disease samples. The transcriptomic signature of human AKI was enriched in pathways involved in cell adhesion, epithelial-to-mesenchymal transition, and cell cycle arrest (eg, CDH6, ITGB6, CDKN1A). In AKI, up-regulation of miR-146a, miR-155, miR-142, and miR-122 was associated with pathways involved in immune cell recruitment, inflammation, and epithelial-to-mesenchymal transition. miR-122 and miR-146 were associated with down-regulation of DDR2 and IGFBP6, which are genes involved in the recovery and progression of kidney disease. These data provide integrated miRNA signatures that complement mRNA and other epigenetic data available in kidney atlases.
急性肾损伤（AKI）是慢性肾脏病（CKD）发生发展的一个重要因素。有必要了解驱动肾脏恢复以及向CKD进展的分子介质。特别是，miRNA在AKI中的调节作用仍知之甚少。在此，我们对在常规护理期间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、微小病变病的受试者，或来自无已知肾脏疾病的肾切除组织。mRNA分析显示，肾切除组织呈现出与AKI相似的损伤特征，而在微小病变病样本中未发现这种特征。人类AKI的转录组特征在参与细胞黏附、上皮-间充质转化和细胞周期阻滞的通路中富集（例如CDH6、ITGB6、CDKN1A）。在AKI中，miR-146a、miR-155、miR-142和miR-122的上调与参与免疫细胞募集、炎症和上皮-间充质转化的通路相关。miR-122和miR-146与DDR2和IGFBP6的下调相关，这两个基因参与肾脏疾病的恢复和进展。这些数据提供了整合的miRNA特征，补充了肾脏图谱中可用的mRNA和其他表观遗传数据。
