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Article: Momordica Charantia Polysaccharides Modulate the Differentiation of Neural Stem Cells via SIRT1/Β-Catenin Axis in Cerebral Ischemia/Reperfusion

TitleMomordica Charantia Polysaccharides Modulate the Differentiation of Neural Stem Cells via SIRT1/Β-Catenin Axis in Cerebral Ischemia/Reperfusion
Authors
KeywordsMomordica charantia polysaccharides (MCPs)
Neural stem cells (NSCs)
Differentiation
SIRT1
β-Catenin
Issue Date2020
PublisherBioMed Central Ltd. The Journal's web site is located at http://www.stemcellres.com
Citation
Stem Cell Research & Therapy, 2020, v. 11 n. 1, p. article no. 485 How to Cite?
AbstractBackground: Stroke is the leading cause of long-term motor disability and cognitive impairment. Recently, neurogenesis has become an attractive strategy for the chronic recovery of stroke. It is important to understand the molecular mechanism that promotes neural stem cell (NSC) neurogenesis for future NSC-based therapies. Our previous study showed that Momordica charantia polysaccharides (MCPs) exerted neuroprotective effects on stroke via their anti-oxidant and anti-inflammation activities. However, it remains unknown whether MCPs promote NSC neurogenesis after cerebral ischemic/reperfusion injury (IRI). Methods: We investigated MCPs’ function in differentiation of neural stem cells (NSCs) in vivo and in vitro experiments. Based on a middle cerebral artery occlusion (MCAO) rat model, the effect of MCPs on neuronal differentiation after MCAO was analyzed. Primary NSCs and neural stem cell line C17.2 were cultured and subjected to glutamate stimulation to establish the cell model of IRI. We evaluated the effect of MCPs on NSC differentiation in IRI cell model by Western blot and immunofluorescence staining. The SIRT1 activity of NSCs post glutamate stimulation was also evaluated by CELL SIRT1 COLORIMETRY ASSAY KIT. In addition, molecular mechanism was clarified by employing the activator and inhibitor of SIRT1. Results: MCPs had no effects on the differentiation of neural stem cells under physiological conditions while shifted NSC differentiation potential from the gliogenic to neurogenic lineage under pathological conditions. Activation of SIRT1 with MCPs was responsible for the neuronal differentiation of C17.2-NSCs. The neuronal differentiation effect of MCPs was attributed to upregulation SIRT1-mediated deacetylation of β-catenin. MCP-induced deacetylation via SIRT1 promoted nuclear accumulation of β-catenin in NSCs. Conclusion: Our findings indicate that the deacetylation of β-catenin by SIRT1 represents a critical mechanism of action of MCPs in promoting NSC neuronal differentiation. It provides an improved understanding of molecular mechanism underlying neuroprotective effects of MCPs in IRI, indicating its potential role on treating ischemic stroke especially chronic recovery.
Persistent Identifierhttp://hdl.handle.net/10722/293788
ISSN
2023 Impact Factor: 7.1
2023 SCImago Journal Rankings: 1.798
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorHu, Z-
dc.contributor.authorLi, F-
dc.contributor.authorZhou, X-
dc.contributor.authorZHANG, F-
dc.contributor.authorHuang, L-
dc.contributor.authorGu, B-
dc.contributor.authorShen, J-
dc.contributor.authorQi, S-
dc.date.accessioned2020-11-23T08:21:48Z-
dc.date.available2020-11-23T08:21:48Z-
dc.date.issued2020-
dc.identifier.citationStem Cell Research & Therapy, 2020, v. 11 n. 1, p. article no. 485-
dc.identifier.issn1757-6512-
dc.identifier.urihttp://hdl.handle.net/10722/293788-
dc.description.abstractBackground: Stroke is the leading cause of long-term motor disability and cognitive impairment. Recently, neurogenesis has become an attractive strategy for the chronic recovery of stroke. It is important to understand the molecular mechanism that promotes neural stem cell (NSC) neurogenesis for future NSC-based therapies. Our previous study showed that Momordica charantia polysaccharides (MCPs) exerted neuroprotective effects on stroke via their anti-oxidant and anti-inflammation activities. However, it remains unknown whether MCPs promote NSC neurogenesis after cerebral ischemic/reperfusion injury (IRI). Methods: We investigated MCPs’ function in differentiation of neural stem cells (NSCs) in vivo and in vitro experiments. Based on a middle cerebral artery occlusion (MCAO) rat model, the effect of MCPs on neuronal differentiation after MCAO was analyzed. Primary NSCs and neural stem cell line C17.2 were cultured and subjected to glutamate stimulation to establish the cell model of IRI. We evaluated the effect of MCPs on NSC differentiation in IRI cell model by Western blot and immunofluorescence staining. The SIRT1 activity of NSCs post glutamate stimulation was also evaluated by CELL SIRT1 COLORIMETRY ASSAY KIT. In addition, molecular mechanism was clarified by employing the activator and inhibitor of SIRT1. Results: MCPs had no effects on the differentiation of neural stem cells under physiological conditions while shifted NSC differentiation potential from the gliogenic to neurogenic lineage under pathological conditions. Activation of SIRT1 with MCPs was responsible for the neuronal differentiation of C17.2-NSCs. The neuronal differentiation effect of MCPs was attributed to upregulation SIRT1-mediated deacetylation of β-catenin. MCP-induced deacetylation via SIRT1 promoted nuclear accumulation of β-catenin in NSCs. Conclusion: Our findings indicate that the deacetylation of β-catenin by SIRT1 represents a critical mechanism of action of MCPs in promoting NSC neuronal differentiation. It provides an improved understanding of molecular mechanism underlying neuroprotective effects of MCPs in IRI, indicating its potential role on treating ischemic stroke especially chronic recovery.-
dc.languageeng-
dc.publisherBioMed Central Ltd. The Journal's web site is located at http://www.stemcellres.com-
dc.relation.ispartofStem Cell Research & Therapy-
dc.rightsStem Cell Research & Therapy. Copyright © BioMed Central Ltd.-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectMomordica charantia polysaccharides (MCPs)-
dc.subjectNeural stem cells (NSCs)-
dc.subjectDifferentiation-
dc.subjectSIRT1-
dc.subjectβ-Catenin-
dc.titleMomordica Charantia Polysaccharides Modulate the Differentiation of Neural Stem Cells via SIRT1/Β-Catenin Axis in Cerebral Ischemia/Reperfusion-
dc.typeArticle-
dc.identifier.emailShen, J: shenjg@hku.hk-
dc.identifier.authorityShen, J=rp00487-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1186/s13287-020-02000-2-
dc.identifier.pmid33198798-
dc.identifier.pmcidPMC7667795-
dc.identifier.scopuseid_2-s2.0-85096049361-
dc.identifier.hkuros320190-
dc.identifier.volume11-
dc.identifier.issue1-
dc.identifier.spagearticle no. 485-
dc.identifier.epagearticle no. 485-
dc.identifier.isiWOS:000594416800005-
dc.publisher.placeUnited Kingdom-

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