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Renal Epo producing Sca-1+ interstitial cells are increased in number after treatment with the anemia drug roxadustat

ABSTRACT: We identify and analyse in detail a specific Sca-1-positive cell population that increases after treatment with the anaemia drug roxadustat and is capable to support Epo production in mice

ORGANISM(S): Mus musculus

PROVIDER: GSE150669 | GEO | 2021/05/14

REPOSITORIES: GEO

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Renal Epo producing Sca-1+ interstitial cells are increased in number after treatment with the anemia drug roxadustat

Project description:Renal Epo producing Sca-1+ interstitial cells are increased in number after treatment with the anemia drug roxadustat

| PRJNA633129 | ENA

Expression profiles of bone marrow cells from model mice for erythropoietin-deficiency anemia (ISAM)

2013-01-18 | GSE43585 | GEO

Receptor-mediated mitophagy regulates EPO production and protects against renal anemia

Project description:Erythropoietin (EPO) drives erythropoiesis and is secreted mainly by the kidney upon hypoxic or anemic stress. The paucity of EPO production in renal EPO-producing cells (REPs) causes renal anemia, one of the most common complications of chronic nephropathies. Although mitochondrial dysfunction is commonly observed in several renal and hematopoietic disorders, the mechanism by which mitochondrial quality control impacts renal anemia remains elusive. In this study, we showed that FUNDC1, a mitophagy receptor, plays a critical role in EPO-driven erythropoiesis induced by stresses. Mechanistically, EPO production is impaired in REPs in Fundc1-/- mice upon stresses, and the impairment is caused by the accumulation of damaged mitochondria, which consequently leads to the elevation of the reactive oxygen species (ROS) level and triggers inflammatory responses by up-regulating proinflammatory cytokines. These inflammatory factors promote the myofibroblastic transformation of REPs, resulting in the reduction of EPO production. We therefore provide a link between aberrant mitophagy and deficient EPO generation in renal anemia. Our results also suggest that the mitochondrial quality control safeguards REPs under stresses, which may serve as a potential therapeutic strategy for the treatment of renal anemia.

2021-05-07 | GSE158361 | GEO

Expression profiles of bone marrow cells from model mice for erythropoietin-deficiency anemia (ISAM)

Project description:We established a novel mouse model for postnatal erythropoietin (Epo)-deficiency anaemia, designated ISAM (inherited super anemic mouse), using a transgenic complementation rescue technique. To identify Epo-regulated genes in vivo, we examined the mRNA expression profile in the bone marrow of ISAM 6 hours after recombinant human EPO (rHuEPO) administration. Erythropoietin-induced gene expression in mouse bone marrow was measured at 6 hours after rHuEPO administration (3,000 U/kg). Three Epo-treated samples were analyzed, and two PBS-treated and one untreated samples were used as a control group.

2013-01-18 | E-GEOD-43585 | biostudies-arrayexpress

Epo producing cell lines

Project description:Generation of mouse renal Epo-producing (REP) cell lines by conditional gene tagging

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Transcriptional profiles of kidneys that underwent reversible UUO model using model mice for erythropoietin-deficiency anemia (ISAM)

2013-03-20 | GSE45304 | GEO

Transcriptional profiles of kidneys that underwent reversible UUO model using model mice for erythropoietin-deficiency anemia (ISAM)

Project description:We have established a novel mouse model for postnatal erythropoietin (Epo)-deficiency anaemia, designated ISAM (inherited super anemic mouse) using a transgenic complementation rescue technique. To identify responsible signals for myofibroblastic transformation of Renal Erythropoietin-producing cells (REPs), we examined the mRNA expression profile of whole ISAM kidneys that underwent reversible UUO model. Unilateral ureteral obstruction (UUO)-induced gene expression changes were analyzed. Three UUO-treated samples (Clip), three reversed UUO kidneys (ClipR-14), and two sham-treated and one untreated samples were compared.

2013-03-20 | E-GEOD-45304 | biostudies-arrayexpress

Integrated Proteomic and Metabolomic Profiling of Urine of Renal Anemia Patients Uncovers Molecular Mechanisms of Roxadustat

Project 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.

2023-03-22 | PXD037002 | Pride

Erythroid progenitors stimulated with EPO

Project description:CD34+ progenitors were isolated from the bone marrow of three healthy volunteers. CD34+CD71+CD45RA- were FACS sorted to enrich for erythroid progenitors. The cells were cultured for four hours with or without EPO in combination with LY294002, and harvested for RNA extraction, amplification and expression analysis. A compound treatment design type is where the response to administration of a compound or chemical (including biological compounds such as hormones) is assayed. Compound Based Treatment: EPO Keywords: compound_treatment_design

2006-11-10 | GSE6260 | GEO

Comparison of gene expression profiles of Sca-1+ and Sca-1- cells post alveolar injury induced by P. aeruginosa

Project description:Alveolar type II cells were isolated from mice before P. aeruginosa injection (basal state) and at 72 h post-PA, and were separated into Sca-1+ and Sca-1- populations. Gene expression profile in the following four groups of cells were compared: non-PA Sca-1-, non-PA Sca-1+, 72 h post-PA Sca-1- and 72 h post-PA Sca-1+.

2014-12-31 | GSE47600 | GEO

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