Renal tubules transcriptome reveals metabolic maladaption during the progression of ischemia-induced acute kidney injury

• Published in: Biochemical and biophysical research communications 2018-10, Vol.505 (2), p.432-438
• Main Authors: Zhang, Difei, Xing, Yuexian, Li, Wenju, Yang, Fan, Lang, Yue, Yang, Jingping, Liu, Zhihong
• Format: Article
• Language: English
• Subjects: 60 APPLIED LIFE SCIENCES; Acute kidney injury; DROPLETS; FIBROSIS; INJURIES; ISCHEMIA; Lipid metabolism; LIPIDS; METABOLISM; MICE; OILS; Progressive renal injury; Renal tubule; RNA; RNA-seq
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2018.08.111

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. •We used the most common AKI model caused by renal ischemia/reperfusion injury (IRI) and established a severe AKI model with progressive renal pathology.•This study is the first to isolate renal tubules and charaterize tubular specific transcriptome during AKI progression.•Tubule specific transcriptome revealed that the deregulation of lipid metabolism occurred in multi-step wise, particularly in the process of lipid transport and FAO inhibition, which may result in TECs apoptosis, dedifferentiation and renal fibrogenesis.