High glucose-increased miR-200c contributes to cellular senescence and DNA damage in neural stem cells.
Birth Defects Res
; 115(18): 1770-1779, 2023 11 01.
Article
em En
| MEDLINE
| ID: mdl-37776548
ABSTRACT
BACKGROUND:
Maternal diabetes increases the risk for neural tube defects (NTDs). It is unclear if miRNAs, senescence, and DNA damage are involved in this process. In this study, we used neural stem cells as an in vitro proxy of embryonic neuroepithelium to investigate whether high glucose triggers neural stem cell senescence and DNA damage by upregulating miR-200c, which may be responsible for NTDs.METHODS:
C17.2 neural stem cells were cultured with normal glucose (5 mM) or high glucose (≥16.7 mM) at different doses and time points for detecting miR-200c levels, markers of senescence and DNA damage. Neural stem cells were exposed to antioxidant SOD1 mimetic Tempol and high glucose for 48 h to test roles of oxidative stress on the miR-200c, senescence, and DNA damage levels. An miR-200c mimic and an inhibitor were transfected into neural stem cells to increase or decrease miR-200c activities.RESULTS:
High glucose upregulated miR-200c in neural stem cells. A time course study of the effect of high glucose revealed that miR-200c initially increased at 12 h and reached its zenith at 18 h. Tempol reduced miR-200c levels caused by high glucose. High glucose induced markers of senescence and DNA damage in neural stem cells. Tempol abolished high glucose-induced markers of senescence and DNA damage. The miR-200c inhibitor suppressed high glucose-induced markers of senescence and DNA damage. Treatment with miR-200c mimic imitates high glucose-induced markers of senescence and DNA damage.CONCLUSIONS:
We show that high glucose increases miR-200c, which contributes to cellular senescence and DNA damage in neural stem cells and provides a potential pathway for maternal diabetes-induced neural tube defects.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Diabetes Gestacional
/
MicroRNAs
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Células-Tronco Neurais
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Defeitos do Tubo Neural
Limite:
Female
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Humans
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Pregnancy
Idioma:
En
Revista:
Birth Defects Res
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
China