Inhibition of METTL14 Alleviates OGD /R‐Induced Neuronal Differentiation Injury in Neural Stem Cells Through Suppressing the Tp53inp2/Ptgs2 Axis: Potential Benefits for the Mouse MCAO Model
Preclinical study demonstrates that METTL14 inhibition rescues neural stem cell differentiation in ischemic stroke models, suggesting a therapeutic target for stroke recovery.
Key Points
To examine the regulatory role of Tp53inp2 and its upstream modulator METTL14 in neural stem cell differentiation following ischemic stroke injury.
Modeled ischemia in vitro using oxygen-glucose deprivation/reperfusion (OGD/R) in primary neural stem cells (NSCs) with targeted knockdown of Tp53inp2 or METTL14 and overexpression of Ptgs2 or Tp53inp2.
Established an in vivo middle cerebral artery occlusion (MCAO) mouse model and injected 5 μL of 5 × 10^5 NSCs transfected with either control or Tp53inp2-targeting shRNA.
Inhibition of Tp53inp2 reduced OGD/R-induced excessive mitophagy and reactive oxygen species levels, which preserved neuronal differentiation in NSCs.
Transplanting Tp53inp2-deficient NSCs into MCAO mice boosted neuronal differentiation, alleviated stroke-induced brain injury, and improved cognitive performance.
METTL14 promoted Tp53inp2 expression via m6A mRNA modification, while METTL14 silencing protected against differentiation injury by downregulating the Tp53inp2/Ptgs2 signaling axis.