Integrated proteomic and metabolomic profiling of urine of renal anemia patients uncovers the molecular mechanisms of roxadustat

You, Xiaoe1; Guo, Baochun1,2,3; Wang, Zhen1,2,3; Ma, Hualin1,2,3; Liu, Lixia1,2,3; Zhou, Ru1,2,3; Zheng, Yaxuan1; Zhang, Xinzhou1,2,3

2023-03-01

10.1039/d3mo00015j

MOLECULAR OMICS   影响因子和分区

2515-4184

Roxadustat (FG-4592) is a hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) prescribed to patients with low hemoglobin associated with chronic kidney disease. Due to the various HIF-mediated adaptive responses, FG-4592 has attracted significant interest for therapeutic use against various diseases. However, the clinical application of Roxadustat remains limited due to a lack of understanding of its underlying mechanisms. Herein, we performed label-free quantitative liquid chromatography with tandem mass spectrometry (LC-MS-MS) proteomics and un-targeted metabolomics to study the protein and metabolite alterations in the urine of renal anemia patients before and after Roxadustat therapy. The results were validated by parallel reaction monitoring (PRM). A total of 46 proteins (including 15 upregulated and 31 downregulated proteins) and 207 metabolites were significantly altered after Roxadustat treatment in urine samples obtained from renal anemia patients. Then, the altered proteins were further validated by PRM. Finally, proteomics combined with metabolomics analysis revealed that the Ras signalling pathway, cysteine and methionine metabolism, arginine and proline metabolism, and cholesterol metabolism were the main pathways altered by Roxadustat treatment. The multi-omics analysis revealed that Roxadustat could alter the protein expression and reverse the potential metabolic changes to exert hypotensive, lipid metabolic regulation, and renoprotective effects in clinical practice.

SCI

英语

通讯

Shenzhen Fund for Guangdong Provincial High-level Clinical Key Specialties[SZGSP001] ; Shenzhen Governmental Sustainable Development Fund[KCXFZ20201221173612034] ; Shenzhen Key Laboratory of Kidney Diseases[ZDSYS201504301616234]

Biochemistry & Molecular Biology

Biochemistry & Molecular Biology

WOS:000968200600001

ROYAL SOC CHEMISTRY

Web of Science

1.Jinan Univ, Shenzhen Peoples Hosp, Clin Med Coll 2, Shenzhen 518020, Guangdong, Peoples R China
2.Jinan Univ, Southern Univ Sci & Technol, Shenzhen Peoples Hosp, Affiliated Hosp 1,Clin Med Coll 2,Dept Nephrol, Shenzhen, Guangdong, Peoples R China
3.Jinan Univ, Southern Univ Sci & Technol, Shenzhen Peoples Hosp, Affiliated Hosp 1,Clin Med Coll 2,Shenzhen Key Lab, Shenzhen, Guangdong, Peoples R China

You, Xiaoe,Guo, Baochun,Wang, Zhen,et al. Integrated proteomic and metabolomic profiling of urine of renal anemia patients uncovers the molecular mechanisms of roxadustat[J]. MOLECULAR OMICS,2023,19(6).

You, Xiaoe.,Guo, Baochun.,Wang, Zhen.,Ma, Hualin.,Liu, Lixia.,...&Zhang, Xinzhou.(2023).Integrated proteomic and metabolomic profiling of urine of renal anemia patients uncovers the molecular mechanisms of roxadustat.MOLECULAR OMICS,19(6).

You, Xiaoe,et al."Integrated proteomic and metabolomic profiling of urine of renal anemia patients uncovers the molecular mechanisms of roxadustat".MOLECULAR OMICS 19.6(2023).