Identification of differentiated expressed genes in cold storage associated kidney transplantation

Background: Though it is acknowledged that ischemia reperfusion injury is the primary pathology of cold storage associated kidney transplantation, its underlying mechanism is not well elucidated. Method: To extend the understanding of molecular event and mine hub genes post-transplantation, we performed bulk RNA-sequencing at different time points (24h, day7 and 14) on a murine kidney transplantation model with prolonged cold storage (10h). Result: In the present study, we showed that genes related to regulation of apoptotic process, DNA damage response, cell cycle/proliferation and inflammatory response were steadily elevated at 24h and day7. The upregulated gene profiling delicately transformed to extracellular matrix organization and fibrosis at day 14. It is prominent that metabolic associated genes persistently took the first place among downregulated genes. The gene ontology terms of particular note to enrich are fatty acid oxidation and mitochondria energy metabolism. Correspondingly, the key enzymes of the above processes were the products of hub genes as recognized. Moreover, we highlighted the proximal tubular cell specific increased genes at 24h by combining the data with public RNA-seq performed on proximal tubules. We also focused on ferroptosis related genes and fatty acid oxidation genes to show profound gene dysregulation in kidney transplantation. Conclusion: The comprehensive characterization of transcriptomic analysis may help provide diagnostic biomarkers and therapeutic targets in kidney transplantation.