PXD037002-2

PXD037002 is an original dataset announced via ProteomeXchange.

Title	Integrated Proteomic and Metabolomic Profiling of Urine of Renal Anemia Patients Uncovers Molecular Mechanisms of Roxadustat
Description	Roxadustat (FG-4592) is a HIF-PHI for patients with low hemoglobin associated with chronic kidney disease. Due to the variety of HIF-mediated adaptive responses, FG-4592 has garnered growing therapeutic interest for use against various diseases, such as kidney and lung injury, obesity and related complications, hypertension, etc. However, the advanced applications of Roxadustat in clinical were limited due to its uncovered mechanisms. In this study, by un-targeted metabolomic and label-free proteomic combining with LC-MS/MS analysis, we identified the differentially expressed proteins and their potential regulatory networks which were correlated with altered metabolites under treatment of Roxadustat, we further performed co-joint analysis, and explored the involved underlying molecular mechanisms of Roxadustat on renal anemia patients. A total of 46 proteins (including 15 up-regulated and 31 down-regulated proteins) and 207 metabolites were significantly altered after Roxadustat treatment on the urine sample obtained from renal anemia patients. Then, the changed proteins were further validated by PRM, by which LTF, CHGA, and RARRES2 were on an upregulated trend, and LRG1, PI16, and VMO1 were on a downregulated trend. Finally, the co-analysis of proteomics combined with metabolomics revealed that the Ras signaling pathway, Cysteine and methionine metabolism, Arginine and proline metabolism, and Cholesterol metabolism are the main affected pathways that are altered by Roxadustat treatment. The multi-omics analysis revealed that Roxadustat can alter the abnormal levels of protein expression and reverse the potential metabolic changes to exert its potential roles in hypotensive, lipid metabolic regulation, and renal functional protection effects in clinical.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:59:05.073.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Xiaoe You
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2022-09-25 15:24:57	ID requested
1	2023-03-21 20:06:54	announced
⏵ 2	2023-11-14 08:59:05	announced	2023-11-14: Updated project metadata.

Dataset with its publication pending

submitter keyword: FG-4592, metabolomic, HIF, proteomic,Roxadustat

Xiaoe You
contact affiliation	The Second Clinical Medical College, Jinan University
contact email	xiaoeyou_jnu_edu@163.com
lab head
Xiaoe You
contact affiliation	Shenzhen People’s Hospital
contact email	xiaoeyou_jnu_edu@163.com
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2023/03/PXD037002

PRIDE project URI

• PRIDE
  1. PXD037002
     1. Label: PRIDE project
     2. Name: Integrated Proteomic and Metabolomic Profiling of Urine of Renal Anemia Patients Uncovers Molecular Mechanisms of Roxadustat