Erythropoietin-Derived Peptide Protects Against Acute Lung Injury After Rat Traumatic Brain Injury

Liu, Yuan; Lu, Junyu; Wang, Xiaoya; Chen, Liu; Liu, Su; Zhang, Zhiren; Yao, Weirong

doi:10.1159/000475434

Cited by 11 publications

(6 citation statements)

References 32 publications

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“…Traumatic acute lung injury (ALI) is characterized by oxidative stress (OS) injury and inflammatory responses, which may lead to mortality (19). Inflammation has been reported to play essential roles in traumatic brain injury (TBI)-induced ALI (24). Currently, conventional mechanical ventilation remains to be a supportive regimen designed to support respiratory function for ALI (1).…”

Section: Introductionmentioning

confidence: 99%

Prophylactic treatment with MSC-derived exosomes attenuates traumatic acute lung injury in rats

Liang

2019

American Journal of Physiology-Lung Cellular and Molecular Phys

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The mesenchymal stem cell (MSC) is a potential strategy in the pretreatment of traumatic acute lung injury (ALI), a disease that causes inflammation and oxidative stress. This study aimed to investigate whether MSC-exosomal microRNA-124-3p (miR-124-3p) affects traumatic ALI. Initially, a traumatic ALI rat model was established using the weight-drop method. Then, exosomes were obtained from MSCs of Sprague-Dawley rats, which were injected into the traumatic ALI rats. We found that miR-124-3p was abundantly-expressed in MSCs-derived exosomes and could directly target purinergic receptor P2X ligand-gated ion channel 7 (P2X7), which was overexpressed in traumatic ALI rats. After that, a loss- and gain-of-function study was performed in MSCs and traumatic ALI rats to investigate the role of miR-124-3p and P2X7 in traumatic ALI. MSC-derived exosomal miR-124-3p or silenced P2X7 was observed to increase the survival rate of traumatic ALI rats and enhance the glutathione/superoxide dismutase activity in their lung tissues. However, the wet/dry weight of lung tissues, activity of methylenedioxyamphetamine and H2O2, and levels of inflammatory factors (TNF-a, IL-6, and IL-8) were reduced. Similarly, the numbers of total cells, macrophages, neutrophils, and lymphocytes in bronchoalveolar lavage fluid were also reduced when treated with exosomal miR-124-3p or silenced P2X7. In conclusion, the results provide evidence that miR-124-3p transferred by MSC-derived exosomes inhibited P2X7 expression, thus improving oxidative stress injury and suppressing inflammatory response in traumatic ALI, highlighting a potential pretreatment for traumatic ALI.

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Section: Introductionmentioning

confidence: 99%

Prophylactic treatment with MSC-derived exosomes attenuates traumatic acute lung injury in rats

Liang

2019

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…As a consequence, IIR may lead to sepsis, systemic inflammatory response syndrome and multiple organ dysfunction syndrome [2]. IIR is also known to cause acute lung injury which in turn leads to a condition known as acute respiratory distress syndrome and contributes to the high mortality associated with IIR [3-5]. The exact participation of IIR in acute lung injury is not clearly understood but is believed to involve the initiation of cell apoptosis through a complex interaction between reactive oxygen species, cytokines and inflammatory mediators [6].…”

Section: Introductionmentioning

confidence: 99%

Nrf2 Activation Induced by Sirt1 Ameliorates Acute Lung Injury After Intestinal Ischemia/Reperfusion Through NOX4-Mediated Gene Regulation

Chai

Zhang

Shen

et al. 2018

Cell Physiol Biochem

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Background/Aims: Nuclear erythroid 2-related factor-2 (Nrf2) is a major stress-response transcription factor that has been implicated in regulating ischemic angiogenesis. We investigated the effects of Nrf2 in regulating revascularization and modulating acute lung injury. Methods: The expression of Nrf2 and sirtuin1 (Sirt1) was assessed in lung tissue by western blotting and immunofluorescence staining after intestinal ischemia/reperfusion (IIR) in Nrf2–/– and wild-type (WT) mice. The involvement of Nrf2 in angiogenesis, cell viability, and migration was investigated in human pulmonary microvascular endothelial cells (PMVECs). Additionally, the influence of Nrf2 expression on NOX pathway activation was measured in PMVECs after oxygen–glucose deprivation/reoxygenation. Results: We found activation and nuclear accumulation of Nrf2 in lung tissue after IIR. Compared to IIR in WT mice, IIR in Nrf2–/– mice significantly enhanced leukocyte infiltration and collagen deposit, and inhibited endothelial cell marker CD31 expression. Nrf2 upregulation and translocation into the nucleus stimulated by Sirt1 overexpression exhibited remission of histopathologic changes and enhanced CD31 expression. Nrf2 knockdown repressed non-phagocytic cell oxidase 4 (NOX4), hypoxia-inducible factor (HIF-1α) and vascular endothelial growth factor (VEGF) expression after IIR. Nrf2 upregulation by Sirt1 enhances NOX4, HIF-1α and VEGF expression after IIR in WT mice. Furthermore, Nrf2 knockdown suppressed cell viability, capillary tube formation and cell migration in PMVECs after oxygen–glucose deprivation/reoxygenation and also inhibited NOX4, HIF-1 and VEGF expression. Moreover, NOX4 knockdown in PMVECs decreased the levels of VEGF, HIF-1α and angiogenesis. Conclusion: Nrf2 stimulation by Sirt1 plays an important role in sustaining angiogenic potential through NOX4-mediated gene regulation.

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“…In mice, iNOS isamong othersexpressed in macrophages and glomerular mesangial cells and inducible by various pro-inflammatory stimuli (77). EPO and pHBSP have been demonstrated to reduce the expression of iNOS either on protein level in AKI of different etiologies (63,78) or on mRNA level in lung and brain injury (79,80). Thus, the reduction in renal nitrotyrosine staining in Stx+EPO and Stx+pHBSP mice could result from an inhibition of iNOS in the glomeruli of these mice.…”

Section: Epo and Phbsp In The Context Of Anemia Correction And Tissue...mentioning

confidence: 99%

Targeting the innate repair receptor axis via erythropoietin or pyroglutamate helix B surface peptide attenuates hemolytic-uremic syndrome in mice

et al. 2022

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Hemolytic-uremic syndrome (HUS) can occur as a systemic complication of infections with Shiga toxin (Stx)-producing Escherichia coli and is characterized by microangiopathic hemolytic anemia and acute kidney injury. Hitherto, therapy has been limited to organ-supportive strategies. Erythropoietin (EPO) stimulates erythropoiesis and is approved for the treatment of certain forms of anemia, but not for HUS-associated hemolytic anemia. EPO and its non-hematopoietic analog pyroglutamate helix B surface peptide (pHBSP) have been shown to mediate tissue protection via an innate repair receptor (IRR) that is pharmacologically distinct from the erythropoiesis-mediating receptor (EPO-R). Here, we investigated the changes in endogenous EPO levels in patients with HUS and in piglets and mice subjected to preclinical HUS models. We found that endogenous EPO was elevated in plasma of humans, piglets, and mice with HUS, regardless of species and degree of anemia, suggesting that EPO signaling plays a role in HUS pathology. Therefore, we aimed to examine the therapeutic potential of EPO and pHBSP in mice with Stx-induced HUS. Administration of EPO or pHBSP improved 7-day survival and attenuated renal oxidative stress but did not significantly reduce renal dysfunction and injury in the employed model. pHBSP, but not EPO, attenuated renal nitrosative stress and reduced tubular dedifferentiation. In conclusion, targeting the EPO-R/IRR axis reduced mortality and renal oxidative stress in murine HUS without occurrence of thromboembolic complications or other adverse side effects. We therefore suggest that repurposing EPO for the treatment of patients with hemolytic anemia in HUS should be systematically investigated in future clinical trials.

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Erythropoietin-Derived Peptide Protects Against Acute Lung Injury After Rat Traumatic Brain Injury

Cited by 11 publications

References 32 publications

Prophylactic treatment with MSC-derived exosomes attenuates traumatic acute lung injury in rats

Prophylactic treatment with MSC-derived exosomes attenuates traumatic acute lung injury in rats

Nrf2 Activation Induced by Sirt1 Ameliorates Acute Lung Injury After Intestinal Ischemia/Reperfusion Through NOX4-Mediated Gene Regulation

Targeting the innate repair receptor axis via erythropoietin or pyroglutamate helix B surface peptide attenuates hemolytic-uremic syndrome in mice

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