Current stem cell research & therapy · 2026
Propofol at a Sedative Dose Potently Activates the G1-S Phase Transition to Promote Neural Stem Cell Proliferation via Down-regulated FoxO3a-p27 Pathway.
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Lan Liangtian, Chen Keyu, Zhang Wen, Sun Shujun, Yang Xiaoyu, Xiong Wei, Xu Xuanxian, Wei Ming, Feng Xia, Lu Dihan
Аннотация
INTRODUCTION: Sedative doses of propofol have recently been reported to exert positive effects on the developing brain, potentially enhancing later cognitive function, but the underlying mechanism remains unclear. This study aims to investigate changes in cell cycle status and reveal the dominant upstream molecular cascade following sedative-dose propofol treatment of primary neural stem cells (NSCs) in vitro.
METHODS: Primary C57BL/6 murine NSCs were isolated and cultured. Proliferation was assessed using CCK-8 assays, direct cell counting, and EdU labeling after exposure to 10 μM propofol. Cell cycle distribution was analyzed by flow cytometry. Bulk RNA sequencing, qRT-PCR, and western blotting were used to explore potential pathways. FoxO3a overexpression via adenovirus was employed to confirm the mechanism.
RESULTS: Primary NSCs, identified with >95% Nestin positivity, were successfully isolated. Propofol at 10 μM enhanced NSC proliferation as assessed by CCK-8 assays, cell counting, and immunofluorescence. Cell cycle analysis revealed that propofol promotes G1-S phase transition in NSCs. FoxO3a, a crucial component of the redox signaling pathway, was down-regulated after propofol exposure, along with its downstream regulator p27. Importantly, FoxO3a overexpression counteracted propofol's effects on cell cycle distribution and NSC proliferation.
DISCUSSION: These findings indicate that propofol promotes NSC proliferation by inhibiting FoxO3a nuclear translocation, a key mechanism driving the G1-S transition. This effect is concentrationdependent and occurs at clinically relevant sedation levels, highlighting its potential neuroprotective role. The cellular context and specific signaling mediators of the FoxO3a-p27 axis warrant further investigation.
CONCLUSION: In summary, this study confirms the FoxO3a-p27 axis as a key pathway mediating propofol's proliferative effects on NSCs at sedative concentrations.
METHODS: Primary C57BL/6 murine NSCs were isolated and cultured. Proliferation was assessed using CCK-8 assays, direct cell counting, and EdU labeling after exposure to 10 μM propofol. Cell cycle distribution was analyzed by flow cytometry. Bulk RNA sequencing, qRT-PCR, and western blotting were used to explore potential pathways. FoxO3a overexpression via adenovirus was employed to confirm the mechanism.
RESULTS: Primary NSCs, identified with >95% Nestin positivity, were successfully isolated. Propofol at 10 μM enhanced NSC proliferation as assessed by CCK-8 assays, cell counting, and immunofluorescence. Cell cycle analysis revealed that propofol promotes G1-S phase transition in NSCs. FoxO3a, a crucial component of the redox signaling pathway, was down-regulated after propofol exposure, along with its downstream regulator p27. Importantly, FoxO3a overexpression counteracted propofol's effects on cell cycle distribution and NSC proliferation.
DISCUSSION: These findings indicate that propofol promotes NSC proliferation by inhibiting FoxO3a nuclear translocation, a key mechanism driving the G1-S transition. This effect is concentrationdependent and occurs at clinically relevant sedation levels, highlighting its potential neuroprotective role. The cellular context and specific signaling mediators of the FoxO3a-p27 axis warrant further investigation.
CONCLUSION: In summary, this study confirms the FoxO3a-p27 axis as a key pathway mediating propofol's proliferative effects on NSCs at sedative concentrations.