| 초록 |
Objectives: This study aimed to identify fibrosis-related metabolites and visualize their spatial distribution in the kidney using spatial metabolomics in a unilateral ureteral obstruction (UUO) mouse model. Methods: UUO was induced in 8-week-old male C57BL/6 mice by ligation of the left ureter, and kidneys were harvested 7 days after surgery. Untargeted metabolomic profiling was performed using liquid chromatography–mass spectrometry (LC-MS) (sham, n=11; UUO, n=13). Spatial metabolite imaging was conducted using Orbitrap secondary ion mass spectrometry (OrbiSIMS) and time-of-flight secondary ion mass spectrometry (TOF-SIMS). Results: LC-MS analysis identified significant alterations in several metabolites in UUO kidneys compared with the sham group, including increased levels of p-cresol sulfate and trimethylamine-N-oxide (TMAO). Lipidomic analysis revealed revealed increased levels of triglycerides and cholesteryl esters, whereas ceramides, sphingomyelins, phosphatidylcholines, and phosphatidylethanolamines were decreased in UUO kidneys. OrbiSIMS imaging detected 272,404 distinct mass-to-charge (m/z) ion signals across kidney sections, enabling high-resolution spatial metabolite mapping. Phosphatidylethanolamines were predominantly distributed in cortical tubular regions and showed reduced signals in UUO kidneys, consistent with LC-MS findings. In contrast, phosphatidylcholines showed localized increases in specific kidney regions despite an overall decrease observed by LC-MS. Conclusion: Spatial metabolomics using OrbiSIMS and TOF-SIMS enabled high-resolution mapping of fibrosis-associated metabolites in the UUO kidney model. The combined use of LC-MS and SIMS imaging provides complementary information on metabolite abundance and spatial localization, offering new insights into metabolic remodeling during renal fibrosis. |