scholarly journals Thrombopoietin Receptor Agonist Eltrombopag Prevents Insulin Resistance and Synaptic Pathology via HIF1α/COX2/Sirt1 Signaling Pathway 

2021 ◽  
Author(s):  
he yu ◽  
xuebao wang ◽  
leping liu ◽  
baihui chen ◽  
shuya feng ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Learning And Memory ◽  
Receptor Agonist ◽  
Synaptic Activity ◽  
Sirtuin 1 ◽  
High Dose ◽  
Thrombopoietin Receptor ◽  
Thrombopoietin Receptor Agonist ◽  
Synaptic Formation

Abstract Background: Insulin resistance has been reported to be closely correlated with the pathogenesis of MHE. The mechanism underlying the effects of thrombopoietin receptor agonist eltrombopag (ELT) on synaptic activity and formation involved in MHE pathogenesis remains unclear. Methods: The effect of ELT on neurodegeneration and insulin resistance was examined in the primary rat neurons and an MHE rat model. Results: We found that the level of thrombopoietin receptor c-MPL (MPL) expression was decreased in MHE brains, and ELT administration improved insulin resistance, alleviated the destruction of synaptic formation and enhanced learning and memory in the MHE rats, indicating the relationship between dowregulated ELT and insulin resistance. Then in vitro, ELT treatment ameliorated the impairment of glucose uptake, indicating the reduction of insulin resistance. High dose of glucose inhibited insulin-stimulated downregulation of Hypoxia-inducible factor-1α (HIF1α) expression, the inhibition of inflammatory response and upregulation of sirtuin-1 (Sirt1), destruction of synaptic formation and activity, which were all reversed by ELT treatment in insulin resistant neurons.Conclusions: These results indicate that ELT is a promising potential therapeutic agent for insulin resistance and defect in learning and memory.

scholarly journals Thrombopoietin receptor agonist eltrombopag prevents insulin resistance-mediated synaptic pathology via HIF1α/GSK3β/Sirt1 pathway

2021 ◽  
Author(s):  
He Yu ◽  
Xuebao Wang ◽  
Leping Liu ◽  
Baihui Chen ◽  
Shuya Feng ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Learning And Memory ◽  
Receptor Agonist ◽  
Sirtuin 1 ◽  
High Dose ◽  
Thrombopoietin Receptor ◽  
Thrombopoietin Receptor Agonist ◽  
Synaptic Pathology ◽  
Synaptic Formation

Abstract Background Minimal hepatic encephalopathy (MHE) is characterized by impaired cognitive function and memory loss, which are often the result of synaptic pathology. Insulin resistance has been reported to be closely correlated with the pathogenesis of MHE. Methods The effect of thrombopoietin receptor agonist eltrombopag (ELT) on neurodegeneration and insulin resistance was examined in the primary rat neurons and an MHE rat model. Results We found that the level of thrombopoietin receptor c-MPL (MPL) expression was decreased in MHE brains, and ELT administration improved insulin resistance, alleviated the destruction of synaptic formation and enhanced learning and memory in the MHE rats, indicating the relationship between dowregulated ELT and insulin resistance. Then in vitro, ELT treatment ameliorated the impairment of glucose uptake, indicating the reduction of insulin resistance. High dose of glucose inhibited insulin-stimulated downregulation of Hypoxia-inducible factor-1α (HIF1α) expression, the phosphorylation of GSK3β (pGSK3 β), upregulation of sirtuin-1 (Sirt1), destruction of synaptic formation and activity, which were all reversed by ELT treatment in insulin resistant neurons. Conclusions These results indicate that ELT is a promising potential therapeutic agent for insulin resistance and defect in learning and memory.

scholarly journals Thrombopoietin receptor agonist eltrombopag alleviates cognitive impairment via NRG1/ErbB4 signaling

2021 ◽  
Author(s):  
jian wang ◽  
leping liu ◽  
xuebao wang ◽  
he yu ◽  
baihui chen ◽  
...  
Keyword(s):  
Protein Expression ◽  
Rat Model ◽  
Receptor Agonist ◽  
Synapse Formation ◽  
Cognitive Impairments ◽  
Sirtuin 1 ◽  
Synaptic Protein ◽  
Thrombopoietin Receptor ◽  
Thrombopoietin Receptor Agonist

Abstract Background Patients with minimal hepatic encephalopathy (MHE) show mild cognitive impairments. Thrombopoietin (TPO) has been shown to be neuroprotective. This study aimed to explore the therapeutic effect of Thrombopoietin receptor agonist eltrombopag (ELT) on MHE and the involvement of NRG1 signaling using primary rat neurons and a MHE rat model. Methods We explored the effects of ELT stimulation on NRG1/ErbB4 signaling and synapse formation in the primary rat neurons. Furthermore, we explored the cerebral TPO expression level and the effect of TPO replacement therapy in an MHE rat model. Results The results showed that ELT stimulation activated NRG1/ErbB4 signaling and enhanced synaptic protein expression in the primary rat neurons via sirtuin 1. An anti-NRG1 antibody, ErbB4 inhibitor, or knockdown of NRG1 or ErbB4 could significantly abolish ELT-induced upregulation of synaptic protein expression in the primary rat neurons. MHE rats had significantly decreased cerebral ELT expression compared with normal rats. ELT activated NRG1/ErbB4 signaling in MHE rat brains. Administration or overexpression of ELT or TPO promoted synapse formation and alleviated cognitive impairments in MHE rats. Conclusions These data suggest that ELT promotes synapse formation in vitro and in vivo via activating NRG1/ErbB4 signaling, serving as a promising therapeutic agent for MHE treatment.

Comparative analyses of the small molecule thrombopoietin receptor agonist eltrombopag and thrombopoietin on in vitro platelet function

2009 ◽  
Vol 37 (9) ◽  
pp. 1030-1037 ◽  
Author(s):  
Joseph A. Erhardt ◽  
Connie L. Erickson-Miller ◽  
Manuel Aivado ◽  
Melanie Abboud ◽  
Kodandaram Pillarisetti ◽  
...  
Keyword(s):  
Small Molecule ◽  
Platelet Function ◽  
Receptor Agonist ◽  
Comparative Analyses ◽  
Thrombopoietin Receptor ◽  
Thrombopoietin Receptor Agonist

Quality of Life Improvements Following Eltrombopag Treatment in Children with Chronic Immune Thrombocytopenia: Case Report

2021 ◽  
Vol 104 (4) ◽  
pp. 672-675
Keyword(s):  
Quality Of Life ◽  
Platelet Count ◽  
Receptor Agonist ◽  
Immune Thrombocytopenia ◽  
Case Series ◽  
Thrombopoietin Receptor ◽  
Thrombopoietin Receptor Agonist ◽  
Low Platelet Count ◽  
Chronic Immune Thrombocytopenia

The present case series described six chronic immune thrombocytopenia patients (cITP), with a median age of 7.7 (7.0 to 13.0) years and low platelet count at 15,500 (7,000 to 20,000)/uL. They were suffering from bleeding symptoms and side effects of treatment. After enrollment, they were treated with thrombopoietin receptor agonist (eltrombopag). Five patients responded positively, showing a median platelet count of 115,000 (39,000 to 433,000)/uL. The median dose of eltrombopag used was 1.3 (0.8 to 2.2) mg/kg/day. The quality of life (QoL) improved for all patients, with their median overall score using a Pediatric QoL questionnaire showing 25.0% improvement. Median scores also showed improvements in each sphere of life functioning as physical (30.8%), emotional (26.4%), social (16.4%), and school (21.4%). The present report demonstrated that a select group of cITP patients, with low platelet count and bleeding symptoms, benefitted from treatment with eltrombopag, as shown by increased platelet counts and improved QoL. Keywords: Chronic ITP, Thrombopoietin receptor agonist, Children

CP-080 Thrombopoietin receptor agonist treatment in idiopathic thrombocytopenic purpura

2015 ◽  
Vol 22 (Suppl 1) ◽  
pp. A32.1-A32
Author(s):  
MH García Lagunar ◽  
I Español Morales ◽  
M Martínez Penella ◽  
I Muñoz García ◽  
M Gutiérrez Cívicos ◽  
...  
Keyword(s):  
Idiopathic Thrombocytopenic Purpura ◽  
Receptor Agonist ◽  
Thrombocytopenic Purpura ◽  
Thrombopoietin Receptor ◽  
Thrombopoietin Receptor Agonist
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