Dataset Information

Label-free quantitative proteomic analysis of serum exosomes from patients of renal anemia: The Good and the Bad of Roxadustat.

ABSTRACT:

Background

Roxadustat is a new oral anti-renal anemia medication that works by stabilizing hypoxia-inducible factor (HIF) which can activate the expression of more than 100 genes in addition to genes related to anemia. However, the more potential molecular targets of roxadustat are not completely clear. Therefore, it is essential to further reveal its molecular targets to guide its clinical applications.

Methods

We performed label-free quantification and LC-MS/MS to study the proteomic alterations in serum exosome of renal anemia patients before and after roxadustat therapy. Results were validated by PRM.

Results

A total of 30 proteins were significantly changed after treatment with roxadustat. Among these proteins, 18 proteins were up-regulated (and 12 were down-regulated). The results are statistically significant (P < 0.05). Then, we validated the result by PRM, the results confirmed that TFRC, HSPA8, ITGB3, COL1A2, and YWHAZ were markedly upregulated, while ITIH2 and CFH were significantly downregulated upon treatment with roxadustat.

Conclusions

TFRC and HSPA8 could be an important target of the action of roxadustat, and roxadustat may increase cardiovascular risk through its influence on platelet activation. Our results provide a theoretical basis for its wider clinical application and preventing expected side effects.

SUBMITTER: You X

PROVIDER: S-EPMC9187900 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Label-free quantitative proteomic analysis of serum exosomes from patients of renal anemia: The Good and the Bad of Roxadustat.

You Xiaoe X Guo Baochun B Wang Zhen Z Ma Hualin H Zhang Xinzhou X

Clinical proteomics 20220611 1

<h4>Background</h4>Roxadustat is a new oral anti-renal anemia medication that works by stabilizing hypoxia-inducible factor (HIF) which can activate the expression of more than 100 genes in addition to genes related to anemia. However, the more potential molecular targets of roxadustat are not completely clear. Therefore, it is essential to further reveal its molecular targets to guide its clinical applications.<h4>Methods</h4>We performed label-free quantification and LC-MS/MS to study the prot ...[more]

PMID: 35690731

Similar Datasets

Project description:BackgroundAlthough renal anemia has attracted widespread attention, a large proportion of chronic kidney disease (CKD) patients with anemia still do not meet the hemoglobin (Hb) targets. The discovery of prolyl hydroxylase domain (PHD) enzymes as regulators of hypoxia-inducible factor (HIF)-dependent erythropoiesis has led to the development of novel therapeutic agents for renal anemia. Roxadustat, the first small-molecule HIF-PHD inhibitor, has completed the phase 3 trials. There are currently more than 15 phase 3 clinical trials worldwide assessing the efficacy and safety of roxadustat in CKD patients with anemia. This review will summarize recent findings of roxadustat in the treatment of renal anemia.SummaryAlthough the administration of erythropoiesis-stimulating agents (ESAs) and iron supplementation are a well-established and highly effective therapeutic approach for renal anemia, there are several safety concerns. Current findings from phase 2 and 3 trials suggest that roxadustat is clinically effective and well tolerated. On the one hand, roxadustat could increase endogenous erythropoietin (EPO) levels within or near physiological range in a titratable manner by inducing HIF pathway activation transiently. On the other hand, roxadustat also improves iron metabolism by decreasing serum hepcidin and increasing intestinal iron absorption, which is beneficial to functional iron deficiency and absolute iron deficiency. More importantly, the erythropoietic response of roxadustat is independent of baseline inflammatory state of CKD patients. Thus, the discovery of roxadustat will revolutionize the treatment strategy for renal anemia.Key messagesRoxadustat is an emerging and promising therapeutic approach against anemia in CKD patients, which differs from those of conventional ESAs. Roxadustat corrects anemia of CKD patients through multiple pathways, beyond elevating EPO levels within physiological range, and also by handling iron metabolism (particularly decreasing the hepcidin levels). Furthermore, the Hb response of roxadustat is independent of the inflammatory microenvironment.

Project description:BackgroundThe high incidence of pre-eclampsia, which affects 2-7% of all pregnancies, remains a major health concern. Detection of pre-eclampsia before the appearance of clinical symptoms is essential to allow early intervention, and would benefit from identification of plasma/serum biomarkers to help guide diagnosis and treatment. Liquid biopsy has emerged as a promising source of protein biomarkers that circumvents some of the inherent challenges of proteome-wide analysis of plasma/serum. In this respect, purified exosomes have the added benefit of being carriers of intercellular communication both in physiological and pathological conditions.MethodsWe compared the protein complement of purified exosomes from three different collections of control and pre-eclamptic serum samples, obtained at the end of the second trimester of pregnancy and at delivery. We employed shotgun label-free proteomics to investigate differential protein expression, which was then validated by targeted proteomics.ResultsWe developed a purification method that yielded highly enriched exosome preparations. The presence of specific pregnancy protein markers suggested that a significant proportion of purified exosomes derived from tissues related to pregnancy. Quantitative proteomic analyses allowed us to identify 10, 114 and 98 differentially-regulated proteins in the three sample collections, with a high degree of concordance. Functional analysis suggested that these proteins participate in biological processes related to pre-eclampsia, including angiogenesis, inflammation and cell migration. The differential abundance of 66 proteins was validated by targeted proteomics. Finally, we studied the impact of the pre-eclampsia-associated exosomes in the proteome using an in vitro cellular model.ConclusionsWe have identified and validated differential exosomal proteins in liquid biopsy of pregnant women that open new possibilities for early detection of pre-eclampsia. Additionally, the functional impact of the proteome composition of purified pre-eclamptic exosomes in target cells provides new information to better understand changes in embryo-maternal interactions and, consequently, the pathogenesis of this disease.

Dataset Information

Label-free quantitative proteomic analysis of serum exosomes from patients of renal anemia: The Good and the Bad of Roxadustat.

Background

Methods

Results

Conclusions

Publications

Label-free quantitative proteomic analysis of serum exosomes from patients of renal anemia: The Good and the Bad of Roxadustat.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets