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Intrarenal metabolomic investigation of chronic kidney disease and its TGF-β1 mechanism in induced-adenine rats using UPLC Q-TOF/HS-MS/MS(E).
MedLine Citation:
PMID:  23227912     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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 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 stimulates 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. The work shows that the metabonomics method is a valuable tool for studying the essence of chronic kidney disease.
Authors:
Ying-Yong Zhao; Xian-Long Cheng; Feng Wei; Xu Bai; Xiao-Jie Tan; Rui-Chao Lin; Qibing Mei
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-12-11
Journal Detail:
Title:  Journal of proteome research     Volume:  -     ISSN:  1535-3907     ISO Abbreviation:  J. Proteome Res.     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-12-11     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101128775     Medline TA:  J Proteome Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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