Integrative Physiology, Department of Medical Cell Biology, Uppsala University , Uppsala , Sweden.
Anaesthesia and Intensive Care Medicine, Department of Surgical Sciences, Uppsala University , Uppsala , Sweden.
Physiol Genomics. 2018 Mar 1;50(3):127-141. doi: 10.1152/physiolgenomics.00037.2017. Epub 2017 Dec 20.
Acute kidney injury (AKI) is a syndrome of reduced glomerular filtration rate and urine production caused by a number of different diseases. It is associated with renal tissue damage. This tissue damage can cause tubular atrophy and interstitial fibrosis that leads to nephron loss and progression of chronic kidney disease (CKD). This review describes the in-common mechanisms behind tissue damage in AKI caused by different underlying diseases. Comparing six high-quality microarray studies of renal gene expression after AKI in disease models (gram-negative sepsis, gram-positive sepsis, ischemia-reperfusion, malignant hypertension, rhabdomyolysis, and cisplatin toxicity) identified 5,254 differentially expressed genes in at least one of the AKI models; 66% of genes were found only in one model, showing that there are unique features to AKI depending on the underlying disease. There were in-common features in the form of four genes that were differentially expressed in all six models, 49 in at least five, and 215 were found in common between at least four models. Gene ontology enrichment analysis could be broadly categorized into the injurious processes hypoxia, oxidative stress, and inflammation, as well as the cellular outcomes of cell death and tissue remodeling in the form of epithelial-to-mesenchymal transition. Pathway analysis showed that MYC is a central connection in the network of activated genes in-common to AKI, which suggests that it may be a central regulator of renal gene expression in tissue injury during AKI. The outlining of this molecular network may be useful for understanding progression from AKI to CKD.
急性肾损伤（AKI）是一种由多种不同疾病引起的肾小球滤过率和尿液生成减少的综合征。它与肾组织损伤有关。这种组织损伤可导致肾小管萎缩和间质纤维化，导致肾单位丢失和慢性肾脏病（CKD）的进展。这篇综述描述了不同基础疾病引起的 AKI 组织损伤的共同机制。对 AKI 后疾病模型（革兰氏阴性菌败血症、革兰氏阳性菌败血症、缺血再灌注、恶性高血压、横纹肌溶解和顺铂毒性）的 6 项高质量微阵列基因表达研究进行比较，在至少一种 AKI 模型中鉴定出 5254 个差异表达基因；66%的基因仅在一种模型中发现，这表明 AKI 具有独特的特征，取决于潜在的疾病。在所有六种模型中差异表达的四个基因、至少五种模型中存在的 49 个基因和至少四种模型中发现的 215 个基因具有共同特征。基因本体富集分析可广泛分为缺氧、氧化应激和炎症等损伤过程，以及上皮细胞向间充质转化等细胞死亡和组织重塑的细胞结果。通路分析表明，MYC 是 AKI 中共同激活基因网络的中心连接，这表明它可能是 AKI 期间肾组织损伤中基因表达的中央调节剂。该分子网络的概述可能有助于理解从 AKI 到 CKD 的进展。
