Dynamic analysis of obstructive nephropathy with prolonged obstruction duration by multi-omics

Introduction It is necessary to study the time series of obstructive nephropathy because of different pathophysiological changes in different stages of obstructive nephropathy. Methods In order to recognize the dynamic molecular changes of obstructive nephropathy, this study applied multi-omics ways to evaluate the mRNA and metabolite in different stage of obstructive nephropathy. Results Based on Gene Ontology (GO) and KEGG pathway analyses of transcriptome and metabolism, we defined specific pathways and persistent pathways in the early, middle, and late stages of obstructive nephropathy. adipocytokine signaling pathway, PPAR signaling pathway, JAK-STAT signaling pathway and all types of amino acid metabolism receive the most attention. Conclusion Through this approach, it was discovered that targeting specific molecules, proteins, kinases and critical pathways could be a promising approach for treating obstructive nephropathy. We have developed a series of unilateral ureteral obstruction (UUO) animal models with varying durations of obstruction to simulate the sequential pathological changes in obstructive nephropathy. The animals were randomly divided into five groups according to the duration of ureter ligation. Group A: ureter ligation lasts for 1 day; Group B: ureter ligation lasts for 3 days; Group C: ureter ligation lasts for 7 days; Group D: ureter ligation lasts for 14 days; Group E: sham group. Rats were anesthetized with ketamine (100 mg/kg). Median laparotomy was conducted on heating pads, and the left ureter was exposed and then ligated with 4-0 silk. The sham group was established by dissecting the left ureter without ligation. The kidneys were harvested on the designated time point day after surgery of each group for transcriptomic and metabolomic analysis. All rats underwent cervical dislocation under anesthesia after the kidneys were removed.