Division of Nephrology, Jinling Hospital, Southern Medical University, Nanjing, China; National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.
National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China; School of Medicine, Southeast University, Nanjing City, Jiangsu Province, China.
Biochem Biophys Res Commun. 2018 Oct 28;505(2):432-438. doi: 10.1016/j.bbrc.2018.08.111. Epub 2018 Sep 25.
Renal tubular epithelial cells (TECs) play a critical role in driving acute kidney injury (AKI) progression, but the key molecular features in TECs during this process is not clear. To better understand the molecular characteristics in renal TECs during AKI and renal fibrogenesis, an irreversible AKI mouse model induced by ischemia/reperfusion injury (IRI) was used in this study. The renal tubules were isolated and tubule specific transcriptome was detected by RNA-seq at different stages in the progression of AKI in this model. The overall transcriptome indicated injury and repair process of TEC after renal IRI. In addition, metabolism maladaption was observed during AKI progression to chronic fibrosis. Particularly, we found dysregulation of multiple steps of lipid metabolism in tubule transcriptomes. Oil red O staining revealed massive lipid droplets accumulation in TECs at day 10, thus confirming the defect of lipid metabolism. This is the first study to charaterize renal tubule specific transcriptome during AKI progression. The results shed light on the molecular features in TECs for progressive AKI.
肾小管上皮细胞（TEC）在推动急性肾损伤（AKI）进展中起着关键作用，但在这个过程中 TEC 中的关键分子特征尚不清楚。为了更好地了解 AKI 和肾纤维化过程中肾 TEC 中的分子特征，本研究使用了由缺血/再灌注损伤（IRI）诱导的不可逆 AKI 小鼠模型。在该模型中 AKI 进展的不同阶段分离肾脏小管，并通过 RNA-seq 检测小管特异性转录组。整体转录组显示了肾 IRI 后 TEC 的损伤和修复过程。此外，在 AKI 进展为慢性纤维化的过程中观察到代谢失调。特别是，我们发现小管转录组中脂质代谢的多个步骤失调。油红 O 染色显示 TEC 在第 10 天大量脂质滴积累，从而证实了脂质代谢的缺陷。这是首次对 AKI 进展过程中肾小管特异性转录组进行的研究。研究结果揭示了 TEC 中渐进性 AKI 的分子特征。
