EPO Derivative ARA290 Attenuates Early Renal Allograft Injury in Rats by Targeting NF-κB Pathway

Liang, Yan; Zhang, H; Gao, Shaobing; Zhu, Guizhen; Zhu, Qing; Gu, Yue; Shao, Fengmin

doi:10.1016/j.transproceed.2018.03.015

Cited by 11 publications

(5 citation statements)

References 34 publications

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“…Previous studies have shown high protective activity of erythropoietin in various experimental pathologies and in many pathological conditions [ 24 , 25 , 26 ]. However, the use of erythropoietin is limited due to the side effects such as erythrocytosis, increased thrombosis, hypertension, growth progression, and the formation of new tumors [ 17 , 24 , 27 ].…”

Section: Discussionmentioning

confidence: 99%

“…The signaling pathway after its activation begins with the phosphorylation of JAK2 [ 29 ]. In other tissues, the heterodimeric receptor (EPOR-βCR) is located, or it is also called the innate repair receptor (IRR) [ 24 , 27 , 30 , 31 ]. The start of the signaling pathway after its activation also begins with the phosphorylation of JAK2; then, the activation of different signaling pathways leads to the implementation of non-erythropoietic effects depending on the tissues [ 30 , 31 , 32 , 33 ].…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Erythropoietin Mimetic Peptide (pHBSP) Corrects Endothelial Dysfunction in a Rat Model of Preeclampsia

Korokin

Гуреев

Гудырев

et al. 2020

IJMS

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Preeclampsia is a severe disease of late pregnancy. Etiological factors and a pathogenetic pattern of events still require significant clarification, but it is now recognized that a large role is played by placentation disorders and emerging endothelial dysfunction. The administration of short-chain peptides mimicking the spatial structure of the B erythropoietin chain may become one of the directions of searching for new drugs for preeclampsia prevention and therapy. Simulation of ADMA-like preeclampsia in Wistar rats was performed by the administration of a non-selective NOS blocker L-NAME from the 14th to 20th day of pregnancy. The administration of the pHBSP at the doses of 10 µg/kg and 250 µg/kg corrected the established morphofunctional disorders. The greatest effect was observed at a dose of 250 µg/kg. There was a decrease in systolic and diastolic blood pressure by 31.2 and 32.8%, respectively (p < 0.0001), a decrease in the coefficient of endothelial dysfunction by 48.6% (p = 0.0006), placental microcirculation increased by 82.8% (p < 0.0001), the NOx concentration was increased by 42,6% (p = 0.0003), the greater omentum edema decreased by 11.7% (p = 0.0005) and proteinuria decreased by 76.1% (p < 0.0002). In addition, there was an improvement in the morphological pattern of the fetoplacental complex and the ratio of BAX to Bcl-2 expression which characterizes the apoptotic orientation of the cells.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Erythropoietin Mimetic Peptide (pHBSP) Corrects Endothelial Dysfunction in a Rat Model of Preeclampsia

Korokin

Гуреев

Гудырев

et al. 2020

IJMS

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“…ARA 290, an 11-amino acid linear nonhematopoietic peptide derived from the three dimensional structure of helix B of the erythropoietin (EPO), interacts selectively with the innate repair receptor (IRR) that arbitrates tissue protection [24,25]. Activation of the IRR by ARA290 commences a local multi antiin ammatory pathways, which inhibit death signal and up-regulate survival signals and subsequently blocks in ammation-induced apoptosis, stimulates tissue restorative functions and produces nitric oxide by endothelial cells and subsequently inhibiting obvious tissue damage [24,26,27]. Besides, activation of the IRR also stimulates tissue repair responses, including free radical scavenging [28].…”

Section: Introductionmentioning

confidence: 99%

An in vivo investigation on the wound-healing activity of Specific ligand for the innate repair receptor, ARA290, using a diabetic animal model

Mashreghi¹,

Bayrami

Sichani

et al. 2023

Preprint

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The diabetic foot ulcer (DFU) are serious problems to diabetes and may be associated with late healing and septic manifestation, consequently result in amputation which is an extortionate incident. The innate repair receptor (IRR) is expressed by injured tissues and is activated by erythropoietin produced and released into damaged tissue. Activation of the IRR might provide benefit for diabetic wound healing. This study evaluated effect of a specific IRR agonist, ARA290, on skin wound repair. The aim of the present study was to evaluate the effect of topical application based on ARA290, in streptozotocin-induced diabetic incision wound models rats. The treatment was performed daily, until day 14 after wound induction. Wound closure was determined and the features of the repaired tissue were examined, including amount of collagen and protein content, biochemical parameters, antioxidant status and proinflammatory cytokines. The data confirmed wound healing activities via macroscopic, biochemical, immunofluorescent and molecular methods. There was meaningful acceleration in wound closure rate, decrease in the period of re-epitalization, greater amount of collagen and protein content in ARA290 treated group when compared with control group. The increase of serum insulin and HDL was divergent with blood glucose decrease and reduced lipid level. The healing effect was confirmed by reduced levels of inflammatory cytokines and lipid peroxidation and augmented antioxidants. The results propose that ARA290-arbitrated IRR activation may signify an appealing approach to treat diabetes-associated wound healing.

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“…The bone marrow megakaryocytes have a homodimeric receptor (EPOR/EPOR) (Lin et al 2017;Huang et al 2018). In other tissues, there is a heterodimeric receptor (EPOR-βCR), so-called the innate repair receptor (IRR) (Culver et al 2017;Lin et al 2017;Wu et al 2017;Yan et al 2018).…”

mentioning

confidence: 99%

Preclinical study of innovative peptides mimicking the tertiary structure of the α-helix B of erythropoietin

Golubev¹,

Гуреев²,

Корокин³

et al. 2020

RRP

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Introduction: The aim of this study was to examine the effectiveness of innovative peptides obtained by addition of polypeptide motifs with antiaggregation activity (Arg-Gly-Asp, Lys-Gly-Asp and Pro-Gly-Pro) to a peptide mimicking the space structure of the α-helix B of erythropoietin pHBSP (Pyr-Glu-Gln-Leu-Glu-Arg-Ala-Leu-Asn-Ser-Ser). Materials and methods: The cytoprotective activity of innovative peptides mimicking the space structure of the α-helix B of erythropoietin at the doses of 5 μg/ml, 30 μg/ml and 50 μg/ml was studied on human endothelial cell culture in a simulated oxidative stress. An ADMA-like model of preeclampsia was simulated in the experiment. The study was conducted in 260 female Wistar rats, weighing 250–300 g. Results and discussion: Innovative peptides mimicking the space structure of the α-helix B of erythropoietin retain their cytoprotective activity in a simulated oxidative stress in HUVEC cell culture at the doses of 5 μg/ml, 30 μg/ml, and 50 μg/ml. The compounds with laboratory codes P-αB1 and P-αB3 had the most pronounced cytoprotective activity. Administration of N-nitro-L-arginine-methyl ether to pregnant females for 7 days causes the morphofunctional changes similar to clinical changes in preeclampsia. The innovative peptide under laboratory code P-αB4 at the dose of 50 μg/kg mimicking the space structure of the α-helix B of erythropoietin shows the most pronounced protective properties. Conclusion: Innovative peptides mimicking the space structure of the α-helix B of erythropoietin have a pronounced positive influence on the morphofunctional disorders in animals with ADMA-like preeclampsia.

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EPO Derivative ARA290 Attenuates Early Renal Allograft Injury in Rats by Targeting NF-κB Pathway

Abstract: ARA290 protects against early renal allograft injury in rats by reducing macrophage infiltration, improving renal morphology, inhibiting mRNA expression of inflammatory mediators, and weakening the binding affinity of NF-κB to DNA.

Cited by 11 publications

References 34 publications

Erythropoietin Mimetic Peptide (pHBSP) Corrects Endothelial Dysfunction in a Rat Model of Preeclampsia

Erythropoietin Mimetic Peptide (pHBSP) Corrects Endothelial Dysfunction in a Rat Model of Preeclampsia

An in vivo investigation on the wound-healing activity of Specific ligand for the innate repair receptor, ARA290, using a diabetic animal model

Preclinical study of innovative peptides mimicking the tertiary structure of the α-helix B of erythropoietin

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