Notch1 signalling inhibits apoptosis of human dental follicle stem cells via both the cytoplasmic mitochondrial pathway and nuclear transcription regulation

摘要: Dental follicle stem cells (DFSCs) have been considered as promising candidate for periodontal tissue regeneration. Understanding the signalling pathways underlying apoptosis of DFSCs will facilitate its biomedical application. Here we showed that Notch1 could inhibit because constitutive overexpression intracellular domain (ICN1) promoted proliferation and suppressed by inhibiting cytoplasmic mitochondrial membrane depolarization, cytochrome c release activation caspase-9 caspase-3. The survival-promoting effect was also accomplished up-regulation anti-apoptotic proteins Bcl-2 Mcl-1, down-regulation pro-apoptotic Bax Bad, blockade multimerization. Moreover, p-Akt (S473) significantly increased after ectopic Notch 1 activation. expression p53 inhibited in Notch1-overexpressing DFSCs, while even when overexpressed. Meanwhile, all opposite phenomena were observed shRNA-silenced DFSCs. Our data strongly suggested via pathway ICN-Akt pathway, together with nuclear gene regulation. These findings would provide molecular cues further medical application