Nitric oxide promotes epidermal stem cell proliferation via FOXG1-c-Myc signalling.
Nitric Oxide
; 73: 1-8, 2018 02 28.
Article
em En
| MEDLINE
| ID: mdl-29248687
ABSTRACT
OBJECTIVE:
Epidermal stem cells (ESCs) play a critical role in wound repair, but the mechanism underlying ESC proliferation is unclear. Here, we explored the effects of nitric oxide (NO) on ESC proliferation and the possible underlying mechanism.METHODS:
The effect of NO (two NO donors, SNAP and spermine NONOate, were used) on cell proliferation was detected using cell proliferation and DNA synthesis assays. Thereafter, expression of FOXG1 and c-Myc induced by NO was determined by immunoblot analysis. pAdEasy-FOXG1 adenovirus and c-Myc siRNA plasmids were infected or transfected, respectively, into human ESCs to detect the effect of FOXG1 and c-Myc on NO-induced cell proliferation. Additionally, NO-induced ESC proliferation in vivo was detected by BrdU incorporation and a superficial second-degree mouse burn model. Moreover, the relationships among NO, FOXG1 and c-Myc were detected by western blotting, real-time PCR and dual luciferase assay.RESULTS:
NO exerted a biphasic effect on ESC proliferation, and 100⯵M SNAP and 10⯵M spermine NONOate were the optimal concentrations to promote cell proliferation. Additionally, NO-promoted human ESC proliferation was mediated by FOXG1 and c-Myc in vitro and vivo. Furthermore, NO regulated FOXG1 expression through cGMP signalling, and NO-induced transcription of c-Myc was regulated by FOXG1-mediated c-Myc promoter activity.CONCLUSION:
This study showed that the biphasic effect of NO on ESC proliferation as well as NO induced ESC proliferation were regulated by the cGMP/FOXG1/c-Myc signalling pathway, suggesting that NO may serve as a new disparate target for wound healing.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Proto-Oncogênicas c-myc
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Fatores de Transcrição Forkhead
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Células Epidérmicas
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Proteínas do Tecido Nervoso
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Óxido Nítrico
Tipo de estudo:
Prognostic_studies
Limite:
Adolescent
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Adult
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Animals
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Child
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Humans
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Male
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article