title: Intrarenal metabolomic investigation of chronic kidney disease and its TGF-β1 mechanism in induced-adenine rats using UPLC Q-TOF/HSMS/MS(E).
abstract: Chronic kidney disease (CKD) is becoming a worldwide public health problem. In this study, a kidney metabonomics method based on the ultra performance liquid chromatography/high-sensitivity mass spectrometry with MS(E) data collection technique was undertaken to explore the excretion pattern of low molecular mass metabolites in rat model of adenine-induced chronic renal failure (CRF). Coupled with blood biochemistry and kidney histopathology results, the significant difference in metabolic profiling between the adenine-induced CRF group and the control group by using pattern recognition analysis indicated that changes in global tissue metabolites were occurred. Some significantly changed metabolites like fatty acids, p-cresol sulfate, and indoxyl sulfate have been identified. The results showed that the most important CRF-related metabolites were polyunsaturated fatty acids, indoxyl sulfate, and p-cresyl sulfate. Indoxyl sulfate and p-cresyl sulfate (uremic toxins) were significantly increased in CRF rats. Indoxyl sulfate and p-cresyl sulfate stimulate progressive tubulointerstitial fibrosis by increasing the expression of transforming growth factor-β1 (TGF-β1). These biochemical changes in tissue metabolites are related to the perturbations of fatty acid metabolism and amino metabolism, which may be helpful to further understand the TGF-β1 mechanisms of tubulointerstitial fibrosis. This work shows that the metabonomics method is a valuable tool for studying the essence of CKD.
authors.affiliation: Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, the College of Life Sciences, Northwest University, No.229 Taibai North Road, Xi'an, Shaanxi 710069, China. zyy@nwu.edu.cn
authors.forename: Ying-Yong
authors.initials: YY
authors.lastname: Zhao
authors.forename: Xian-Long
authors.initials: XL
authors.lastname: Cheng
authors.forename: Feng
authors.initials: F
authors.lastname: Wei
authors.forename: Xu
authors.initials: X
authors.lastname: Bai
authors.forename: Xiao-Jie
authors.initials: XJ
authors.lastname: Tan
authors.forename: Rui-Chao
authors.initials: RC
authors.lastname: Lin
authors.forename: Qibing
authors.initials: Q
authors.lastname: Mei
mesh_terms: D000225:Adenine; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003408:Cresols / Q000652:urine; D005231:Fatty Acids, Unsaturated / Q000652:urine; D005355:Fibrosis; D015870:Gene Expression; D007200:Indican / Q000652:urine; D007677:Kidney Function Tests; D007684:Kidney Tubules / Q000737:chemistry* / Q000473:pathology; D008297:Male; D055442:Metabolome; D051381:Rats; D051436:Renal Insufficiency, Chronic / Q000139:chemically induced / Q000473:pathology* / Q000652:urine*; D013463:Sulfuric Acid Esters / Q000652:urine; D053719:Tandem Mass Spectrometry; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D003408:Cresols; D005231:Fatty Acids, Unsaturated; D013463:Sulfuric Acid Esters; D053773:Transforming Growth Factor beta1; C408690:4-cresol sulfate; D000225:Adenine; D007200:Indican