CUEDC2 ablation enhances the efficacy of mesenchymal stem cells in ameliorating cerebral ischemia/reperfusion insult
Mesenchymal stem cell (MSC) therapy has been reported to be a promising therapeutic option for cerebral ischemia/reperfusion (I/R) insult. However, the poor survival rate of engrafted MSCs under unfavorable cerebral I/R-induced microenvironment inhibits their efficiency during clinical application. CUE domain-containing 2(CUECD2) exhibits its protective role on cardiomyocytes by mediating the antioxidant capacity. Our study explored the functional role of CUEDC2 in cerebral I/R challenge and determined whether CUECD2-modified MSCs could improve the efficacy of treatment of the insulted neurons. We also evaluated the possible mechanisms involved in cerebral I/R condition. Cerebral I/R stimulation suppressed CUEDC2 levels in brain tissues and neurons. siRNA-CUEDC2 in neurons significantly inhibited cerebral I/R-induced apoptosis and oxidative stress levels invitro. Moreover, siRNA-CUEDC2 in the MSCs group remarkably enhanced the therapeutic efficacies in cerebral I/R-induced neuron injury and brain tissue impairment when compared to the non-genetic MSCs treatment group. At the molecular level, siRNA-CUEDC2 in MSCs markedly enhanced its antioxidant and anti-inflammatory effect in co-cultured neurons by upregulating glutathione peroxidase 1 (GPX1) expression levels while suppressing NF-kB activation. These findings provide a novel strategy for the utilization of MSCs to promote cerebral ischemic stroke outcomes.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:13 |
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| Enthalten in: |
Aging - 13(2021), 3 vom: 20. Jan., Seite 4335-4356 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Huang, Yan [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 16.08.2021 Date Revised 07.12.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.18632/aging.202394 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM320561127 |
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| 245 | 1 | 0 | |a CUEDC2 ablation enhances the efficacy of mesenchymal stem cells in ameliorating cerebral ischemia/reperfusion insult |
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| 500 | |a Date Revised 07.12.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Mesenchymal stem cell (MSC) therapy has been reported to be a promising therapeutic option for cerebral ischemia/reperfusion (I/R) insult. However, the poor survival rate of engrafted MSCs under unfavorable cerebral I/R-induced microenvironment inhibits their efficiency during clinical application. CUE domain-containing 2(CUECD2) exhibits its protective role on cardiomyocytes by mediating the antioxidant capacity. Our study explored the functional role of CUEDC2 in cerebral I/R challenge and determined whether CUECD2-modified MSCs could improve the efficacy of treatment of the insulted neurons. We also evaluated the possible mechanisms involved in cerebral I/R condition. Cerebral I/R stimulation suppressed CUEDC2 levels in brain tissues and neurons. siRNA-CUEDC2 in neurons significantly inhibited cerebral I/R-induced apoptosis and oxidative stress levels invitro. Moreover, siRNA-CUEDC2 in the MSCs group remarkably enhanced the therapeutic efficacies in cerebral I/R-induced neuron injury and brain tissue impairment when compared to the non-genetic MSCs treatment group. At the molecular level, siRNA-CUEDC2 in MSCs markedly enhanced its antioxidant and anti-inflammatory effect in co-cultured neurons by upregulating glutathione peroxidase 1 (GPX1) expression levels while suppressing NF-kB activation. These findings provide a novel strategy for the utilization of MSCs to promote cerebral ischemic stroke outcomes | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a CUEDC2 | |
| 650 | 4 | |a MCAO | |
| 650 | 4 | |a MSCs | |
| 650 | 4 | |a OGD/R | |
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| 700 | 1 | |a Xiao, Han |e verfasserin |4 aut | |
| 700 | 1 | |a Hu, Zhiping |e verfasserin |4 aut | |
| 700 | 1 | |a Tan, Fengbo |e verfasserin |4 aut | |
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