Erythropoietin as an antiapoptotic, tissue-protective cytokine

Ghezzi, Pietro; Brines, Michael

doi:10.1038/sj.cdd.4401450

Cited by 306 publications

(256 citation statements)

References 92 publications

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“…Beyond its hematopoietic properties, EPO modulates a broad array of vital cellular processes including progenitor stem cell development, cellular integrity, and angiogenesis [8,9] . Additionally, in various tissues, EPO inhibits the apoptotic mechanisms of injury, including preservation of cellular membrane asymmetry to prevent inflammation [10][11][12] . Experimental evidence supports a vigorous cytoprotective effect and EPO is now considered to have applicability in a variety of disorders, such as cerebral ischemia, myocardial infarction, and chronic congestive heart failure [12][13][14][15] .…”

Section: Basic Researchmentioning

confidence: 99%

“…EPO inhibits the apoptotic mechanisms of injury, including preservation of cellular membrane asymmetry to prevent inflammation, can therefore be regarded as a general tissue-protective cytokine [11,12,14] . Agents that can prevent apoptosis can be effective long after the occurrence of injury [5] .…”

Section: A B C Dmentioning

confidence: 99%

“…EPO plays a dual role in vascular protection by preserving endothelial cell integrity [6,8,9] , thus playing a role in maintaining the integrity of microvasculature [11] . One of the major factors for the development of alveolar edema in ANP is the increased microvascular permeability.…”

Section: A B C Dmentioning

confidence: 99%

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Protective effects of erythropoietin against acute lung injury in a rat model of acute necrotizing pancreatitis

Oge¹,

Tascilar²,

Güldeniz³

et al. 2007

WJG

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RESULTS:The mean pleural effusion volume, calculated LW/BW ratio, serum IL-6 and lung tissue MDA levels were significantly lower in EPO groups than in ANP groups. No statistically significant difference was observed in either serum or tissue values of IL-2 among the groups. The level of tumor necrosis factor-α (TNF-α) and IL-6 and accumulation of ox-LDL were evident in the lung tissues of ANP groups when compared to EPO groups, particularly at 72 h. Histopathological evaluation confirmed the improvement in lung injury parameters after exogenous EPO administration, particularly at 48 h and 72 h. C O N C L U S I O N : E P O a d m i n i s t r a t i o n l e a d s t o asignificant decrease in ALI parameters by inhibiting polymorphonuclear leukocyte (PMNL) accumulation, decreasing the levels of proinflammatory cytokines in circulation, preserving microvascular endothelial cell integrity and reducing oxidative stress-associated lipid peroxidation and therefore, can be regarded as a cytoprotective agent in ANP-induced ALI. INTRODUCTIONAcute pancreatitis (AP) is a life-threatening necroinflammatory disease with significant morbidity and mortality rates, especially when complicated by systemic inflammatory response syndrome (SIRS) and multiple organ failure (MODS) [1,2] . Death occurs in 60% of the patients within the first 6 d of disease onset and pulmonary complications including acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) Abstract AIM: To investigate the effect of exogenous erythropoietin (EPO) administration on acute lung injury (ALI) in an experimental model of sodium taurodeoxycholateinduced acute necrotizing pancreatitis (ANP). BASIC RESEARCH METHODS:Forty-seven male Wistar albino rats were randomly divided into 7 groups: sham group (n = 5), 3 ANP groups (n = 7 each) and 3 EPO groups (n = 7 each). ANP was induced by retrograde infusion of 5% sodium taurodeoxycholate into the common bile duct. Rats in EPO groups received 1000 U/kg intramuscular EPO immediately after induction of ANP. Rats in ANP groups were given 1 mL normal saline instead. All animals were sacrificed at postoperative 24 h, 48 h and 72 h. Serum amilase, IL-2, IL-6 and lung tissue malondialdehyde (MDA) were measured. Pleural effusion volume and lung/body weight (LW/BW) ratios were calculated. Tissue levels of TNF-α, IL-2 and IL-6 were screened immunohistochemically. Additionally, ox-LDL accumulation was assessed with immune-fluorescent staining. Histopathological alterations in the lungs were also scored.

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Section: Basic Researchmentioning

confidence: 99%

Section: A B C Dmentioning

confidence: 99%

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Protective effects of erythropoietin against acute lung injury in a rat model of acute necrotizing pancreatitis

Oge¹,

Tascilar²,

Güldeniz³

et al. 2007

WJG

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“…In neurodegeneration, hMSC could serve as a vehicle to deliver EPO protein into injured tissues as recombinant EPO could not pass through the bloodbrain barrier. While high concentrations of recombinant EPO could be administered intravenously to enable some protein to reach the injured sites, there are also risks of thrombosis and hypertension to be considered (Baskin and Lasker 1990;Ghezzi and Brines 2004;Lieutaud et al 2008;Loo and Beguin 1999). Local delivery of EPO by MSC has manifested a more potent therapeutic effect for treatment of myocardium infarct (Copland et al 2008) and cerebral ischemia (Esneault et al 2008) than with delivery of MSC or EPO alone in in vivo studies.…”

Section: Discussionmentioning

confidence: 99%

Extended and stable gene expression via nucleofection of MIDGE construct into adult human marrow mesenchymal stromal cells

et al. 2011

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Human mesenchymal stromal cell (hMSC) is a potential target for cell and gene therapy-based approaches against a variety of different diseases. Whilst cationic lipofection has been widely experimented, the Nucleofector technology is a relatively new non-viral transfection method designed for primary cells and hard-to-transfect cell lines. Herein, we compared the efficiency and viability of nucleofection with cationic lipofection, and used the more efficient transfection method, nucleofection, to deliver a construct of minimalistic, immunologically defined gene expression encoding the erythropoietin (MIDGE-EPO) into hMSC. MIDGE construct is relatively safer than the viral and plasmid expression systems as the detrimental eukaryotic and prokaryotic gene and sequences have been eliminated. Using a plasmid encoding the luciferase gene, we demonstrated a high transfection efficiency using the U-23 (21.79 ± 1.09%) and C-17 (5.62 ± 1.09%) pulsing program in nucleofection. The cell viabilities were (44.93 ± 10.10)% and (21.93 ± 5.72)%, respectively 24 h post-nucleofection. On the other hand, lipofection treatment only yielded less than 0.6% efficiencies despite showing higher viabilities. Nucleofection did not affect hMSC renewability, immunophenotype and differentiation potentials. Subsequently, we nucleofected MIDGE-EPO using the U-23 pulsing program into hMSC. The results showed that, despite a low nucleofection efficiency with this construct, the EPO protein was stably expressed in the nucleofected cells up to 55 days when determined by ELISA or immunocytochemical staining. In conclusion, nucleofection is an efficient non-viral transfection approach for hMSC, which when used in conjunction with a MIDGE construct, could result in extended and stable transgene expression in hMSC.

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“…The antiapoptotic and cytoprotective effect of erythropoietin on neurons (36) and cardiomyocyte cells (37) is also mediated via the EpoR. In this regard, erythropoietin binds to the extracellular domain of the EpoR, which is a single transmembrane protein that lacks protein tyrosine kinase or other enzymatic activity.…”

Section: Discussionmentioning

confidence: 99%

Erythropoietin inhibits apoptosis induced by photodynamic therapy in ovarian cancer cells

Solár

Kovaľ

Mikeš

et al. 2008

Molecular Cancer Therapeutics

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Recombinant human erythropoietin is widely used to treat anemia associated with cancer and with the myelosuppressive effects of chemotherapy, particularly platinumbased regimens. Erythropoietin is the principal regulator of erythroid cell proliferation, differentiation, and apoptosis. Recently, the antiapoptotic and proliferative effects of erythropoietin on nonhematopoietic cells were also established. We now show the effect of erythropoietin treatment on the response of A2780 and SKOV3 ovarian carcinoma cell lines to photodynamic therapy (PDT) using hypericin. SKOV3 exhibited an increased resistance to hypericin when cells were treated with erythropoietin. This resistance was reversed by treatment of SKOV3 cells with the specific Janus kinase 2 kinase inhibitor AG490 or the tyrosine kinase inhibitor genistein. These results support a role for the specific erythropoietin-induced Janus kinase 2/STAT signal transduction pathway in PDT resistance. Evidence of erythropoietin signaling was obtained by the demonstration of Akt phosphorylation in both A2780 and SKOV3 cells. Erythropoietin-treated SKOV3 cells exhibited decreased apoptosis induced by hypericin, an effect that was blocked by the phosphoinositide 3-kinase/Akt inhibitor wortmannin. These results may have important implications for ovarian cancer patients undergoing PDT and receiving erythropoietin.

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Erythropoietin as an antiapoptotic, tissue-protective cytokine

Cited by 306 publications

References 92 publications

Protective effects of erythropoietin against acute lung injury in a rat model of acute necrotizing pancreatitis

Protective effects of erythropoietin against acute lung injury in a rat model of acute necrotizing pancreatitis

Extended and stable gene expression via nucleofection of MIDGE construct into adult human marrow mesenchymal stromal cells

Erythropoietin inhibits apoptosis induced by photodynamic therapy in ovarian cancer cells

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