Expression profiles of bone marrow cells from model mice for erythropoietin-deficiency anemia (ISAM)
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE43585 | GEO | 2013/01/18
SECONDARY ACCESSION(S): PRJNA186802
REPOSITORIES: GEO
Similar Datasets
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.
2013-03-20 | GSE45304 | GEO
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
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
Project description:Resistance to erythropoietin (EPO) treatment is observed in a considerable proportion of anemic patients with chronic kidney disease. Previous reports suggest that inflammation is one of the major independent predictors of this resistance, and pro-inflammatory cytokines have been shown to inhibit erythropoiesis. The aim of this study was to investigate EPO-induced modification to gene expression in primary cultured leukocytes. Microarray experiments were performed on ex vivo Peripheral Blood Mononuclear Cells (PBMCs) from pooled ten healthy donors (n=9), primed or not with TNF-alpha, and treated with recombinant human erythropoietin alpha (EPO-alpha). Real-time PCR experiments were used to validate expression of the molecular targets considered most relevant for inflammation. Data analysis suggested that EPO-alpha treatment mainly modulated genes involved in cell movement and cell-cell interaction in primed PBMCs. Notably, EPO-alpha exerts anti-inflammatory effects inhibiting the expression of pro-inflammatory cytokine IL-8 and its receptor CXCR2; by contrast, EPO-alpha further increases expression of genes relating to promotion of inflammation encoding for IL-1beta and CCL8, and induces de novo synthesis of IL-1alpha, CXCL1 and CXCL5 in primed PBMCs. MAPK p38alpha?reducing activity is involved in modulation of IL-1beta and IL-8 expression. In conclusion, our findings confirm the anti-inflammatory role for EPO, but also suggest a plausible in vivo scenario, in which the positive correlation found between EPO-resistance and elevated levels of some pro-inflammatory mediators is due to treatment with EPO itself. One future objective will be to perform in vivo measurement of the molecular targets highlighted, in order to identify any additional markers involved in EPO-resistance among hypo-responsive patients.
2013-12-19 | GSE53336 | GEO
Project description:Resistance to erythropoietin (EPO) treatment is observed in a considerable proportion of anemic patients with chronic kidney disease. Previous reports suggest that inflammation is one of the major independent predictors of this resistance, and pro-inflammatory cytokines have been shown to inhibit erythropoiesis. The aim of this study was to investigate EPO-induced modification to gene expression in primary cultured leukocytes. Microarray experiments were performed on ex vivo Peripheral Blood Mononuclear Cells (PBMCs) from pooled ten healthy donors (n=9), primed or not with TNF-alpha, and treated with recombinant human erythropoietin alpha (EPO-alpha). Real-time PCR experiments were used to validate expression of the molecular targets considered most relevant for inflammation. Data analysis suggested that EPO-alpha treatment mainly modulated genes involved in cell movement and cell-cell interaction in primed PBMCs. Notably, EPO-alpha exerts anti-inflammatory effects inhibiting the expression of pro-inflammatory cytokine IL-8 and its receptor CXCR2; by contrast, EPO-alpha further increases expression of genes relating to promotion of inflammation encoding for IL-1beta and CCL8, and induces de novo synthesis of IL-1alpha, CXCL1 and CXCL5 in primed PBMCs. MAPK p38alpha?reducing activity is involved in modulation of IL-1beta and IL-8 expression. In conclusion, our findings confirm the anti-inflammatory role for EPO, but also suggest a plausible in vivo scenario, in which the positive correlation found between EPO-resistance and elevated levels of some pro-inflammatory mediators is due to treatment with EPO itself. One future objective will be to perform in vivo measurement of the molecular targets highlighted, in order to identify any additional markers involved in EPO-resistance among hypo-responsive patients. In this study, we analyzed the expression profiles of pooled blood PBMCs from 10 healthy donors primed or not with TNF-alpha and then treated with EPO-alpha. All RNAs from no stimulated PBMCs were hybridized against RNAs from PBMCs treated with TNF-alpha or TNF-alpha and EPO-alpha. We performed a total of 9 technical replicates.
2013-12-19 | E-GEOD-53336 | biostudies-arrayexpress
Project description:Abstract Background: Several studies on the use of erythropoietin (Epo) to treat anaemia in patients undergoing cancer treatment have shown adverse effects on tumour control and survival. Experimental studies indicate that this could be linked to an interaction with wound healing processes and not an effect on tumour cells per se. We have previously shown that erythropoietin in combination with surgical trauma stimulates tumour growth. In the present study, we investigated the effect of surgery and Epo on gene expression. Methods: Human tumours from oral squamous cell cancer were xenotransplanted to nude mice treated with Epo. The tumours were then transected in a standardised procedure to mimic surgical trauma and the change in gene expression of the tumours was investigated by microarray analysis. qRT-PCR was used to measure the levels of mRNAs of pro-apoptotic genes. The frequency of apoptosis in the tumours was assessed using immunohistochemistry for caspase-3. Results: There was little change in the expression of genes involved in tumour growth and angiogenesis but a significant down-regulation of the expression of genes involved in apoptosis. This effect on apoptosis was confirmed by a general decrease in the expression of mRNA for selected pro-apoptotic genes. Epo-treated tumours had a significantly lower frequency of apoptosis as measured by immunohistochemistry for caspase 3. Conclusions: Our results suggest that the increased tumour growth during erythropoietin treatment might be due to inhibition of apoptosis, an effect that becomes significant during tissue damage such as surgery. This further suggests that the decreased tumour survival during erythropoietin treatment might be due to inhibition of apoptosis. Key words: Erythropoietin, Head and neck cancer, surgery, apoptosis, wound healing, xenograft.
2014-06-04 | GSE58194 | GEO
Project description:Abstract Background: Several studies on the use of erythropoietin (Epo) to treat anaemia in patients undergoing cancer treatment have shown adverse effects on tumour control and survival. Experimental studies indicate that this could be linked to an interaction with wound healing processes and not an effect on tumour cells per se. We have previously shown that erythropoietin in combination with surgical trauma stimulates tumour growth. In the present study, we investigated the effect of surgery and Epo on gene expression. Methods: Human tumours from oral squamous cell cancer were xenotransplanted to nude mice treated with Epo. The tumours were then transected in a standardised procedure to mimic surgical trauma and the change in gene expression of the tumours was investigated by microarray analysis. qRT-PCR was used to measure the levels of mRNAs of pro-apoptotic genes. The frequency of apoptosis in the tumours was assessed using immunohistochemistry for caspase-3. Results: There was little change in the expression of genes involved in tumour growth and angiogenesis but a significant down-regulation of the expression of genes involved in apoptosis. This effect on apoptosis was confirmed by a general decrease in the expression of mRNA for selected pro-apoptotic genes. Epo-treated tumours had a significantly lower frequency of apoptosis as measured by immunohistochemistry for caspase 3. Conclusions: Our results suggest that the increased tumour growth during erythropoietin treatment might be due to inhibition of apoptosis, an effect that becomes significant during tissue damage such as surgery. This further suggests that the decreased tumour survival during erythropoietin treatment might be due to inhibition of apoptosis. Key words: Erythropoietin, Head and neck cancer, surgery, apoptosis, wound healing, xenograft. We wanted to study the effect of wound healing mechanisms on remaining tumour tissue efter incomplete surgery or biopsy. We xenografted human Head and Neck squamous Cell Cancer (HNSCC) tumours on Balb/c nude mice. The mice were divided in six groups. Three of the groups received intrapertoneal doses of erythropoietin (Epo) and the other three groups were given NaCl as placebo. One treated and one non-treated group were harvested without surgical transection. In the other four groups, the tumours were transected mimicking subtotal surgery. One Epo-treated and one non-treated group was analysed after 24 hours after transection and the remaining two groups 48 hours after surgery. Groups C and D were not analyzed due to harvesting at an unsuitable time interval. Group A No surgery (=FALSE) + Epo Group B No surgery (=FALSE) + NaCl Group E Surgery (=TRUE) + Epo 24 hours after surgical transection Group F Surgery (=TRUE) + NaCl 24 hours after surgical resection Group G Surgery (=TRUE) + Epo 48 hours after surgical transection Group H Surgery (=TRUE) + Nacl 48 hours after surgical transection
2014-06-04 | E-GEOD-58194 | biostudies-arrayexpress
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
Project description:Erythropoietin (EPO) has multiple functions beyond stimulating erythrocytosis, including modulation of T cell immunity. Effects EPO in transplantation and associated mechanisms remain incompletely understood. We analyzed outcomes and performed cellular and molecular mechanistic assessments in murine wild type (WT) and conditional EPO receptor (EPOR) knockout recipients of cardiac allografts. In translational studies, we tested EPO’s effects in a non-human primate system.
2023-03-01 | GSE199270 | GEO
Project description:Erythropoietin (EPO) is the primary regulator of erythropoiesis in the mammalian fetus and the adult through interaction with erythropoietin receptor (EPOR). Deficiency of EPO induces anemia that is a major cause of death in patients with chronic kidney disease. Thus, development of safe treatment for anemia is an urgent issue. In this study, we investigated the effect of γ-aminobutyric acid (GABA) on serum EPO level and erythropoiesis, and its mechanism was elucidated in rat. GABA significantly (P < 0.05) increased EPO level in serum and expression levels of EPO and EPOR in a dose dependent manner. GABA increased the expression levels of HIF-1 and HIF-2 in a dose dependent manner compared with the negative control; while GABA did not affect the expression of prolyl-hydroxylase domain protein-2α (PHD-2α) gene, an oxygen sensor. GABA supplementation alters energy production pathway resulted in hypoxic condition, which increases EPO level in rat through overexpression of HIF-1 and HIF-2. This study shows a new physiological role of GABA in EPO production and thus GABA could contribute to the prevention of anemia by using alone or in combination with other anemia treating drugs.
2020-03-04 | GSE146299 | GEO