Cuevas-Delgado Paula, Miguel Verónica, Lamas Santiago, Barbas Coral, Rupérez Francisco J
Centre for Metabolomics and Bioanalysis (CEMBIO), School of Pharmacy, Universidad San Pablo-CEU, CEU Universities, Urbanización Montepríncipe, Boadilla del Monte, Madrid 28660, Spain.
Program of Physiological and Pathological Processes, Centro de Biología Molecular "Severo Ochoa" (CBMSO, CSIC-UAM), c. Nicolás Cabrera 1, Madrid 28049, Spain.
Int J Mol Sci. 2025 May 21;26(10):4933. doi: 10.3390/ijms26104933.
In chronic kidney disease (CKD) research, animal models such as the unilateral ureteral obstruction (UUO) rodent model are crucial to understanding disease progression, particularly renal fibrosis. Despite its widespread use, the molecular mechanisms driving CKD remain incompletely understood. Given the interplay between metabolism and fibrosis, a comprehensive metabolomic analysis of UUO renal tissue is necessary. This study involved untargeted multiplatform analysis using liquid chromatography (LC), gas chromatography (GC), and capillary electrophoresis (CE) coupled with mass spectrometry (MS) to examine murine kidney tissue from the UUO model. The results highlight metabolic changes associated with tubulointerstitial fibrosis, which affect pathways such as the tricarboxylic acid (TCA) cycle, the urea cycle, and lipid metabolism. In particular, fibrosis impacts the lipidomic profile, with decreases in most lipid classes and increases in specific glycerophospholipids, hexosylceramides, and cholesterol esters. These findings demonstrate the value of a multiplatform approach in elucidating metabolic alterations in CKD, providing information on the underlying molecular mechanisms and paving the way for further research.
在慢性肾脏病(CKD)研究中,诸如单侧输尿管梗阻(UUO)啮齿动物模型等动物模型对于理解疾病进展,尤其是肾纤维化至关重要。尽管其被广泛使用,但驱动CKD的分子机制仍未被完全理解。鉴于代谢与纤维化之间的相互作用,对UUO肾组织进行全面的代谢组学分析是必要的。本研究采用液相色谱(LC)、气相色谱(GC)和毛细管电泳(CE)结合质谱(MS)的非靶向多平台分析方法,对UUO模型的小鼠肾组织进行检测。结果突出了与肾小管间质纤维化相关的代谢变化,这些变化影响三羧酸(TCA)循环、尿素循环和脂质代谢等途径。特别是,纤维化影响脂质组学特征,大多数脂质类别减少,而特定的甘油磷脂、己糖神经酰胺和胆固醇酯增加。这些发现证明了多平台方法在阐明CKD代谢改变方面的价值,为潜在分子机制提供了信息,并为进一步研究铺平了道路。