自噬
衰老
细胞凋亡
细胞生物学
基因敲除
下调和上调
化学
生物
基因
生物化学
作者
Caichun Yue,Yinghui Wu,Yanzhang Xia,Tianwen Xin,Yuhao Gong,Linfeng Tao,Cong Shen,Yue Zhu,Minghong Shen,Donglai Wang,Jun Shen
出处
期刊:Research Square - Research Square
日期:2023-10-28
标识
DOI:10.21203/rs.3.rs-3481551/v1
摘要
Abstract Intervertebral disc degeneration (IDD) is a significant cause of low back pain, characterized by excessive senescence and apoptosis of nucleus pulposus cells (NPCs). However, the precise mechanisms behind this senescence and apoptosis remains unclear. This study aimed to investigate the role of Tbxt in IDD both in vitro and in vivo, using a hydrogen peroxide (H2O2)-induced NPCs senescence and apoptosis model, as well as a rat acupuncture IDD model. Firstly, the expression of p16 and cleaved-caspase 3 significantly increased in degenerated human NPCs, accompanied by a decrease in Tbxt expression. Knockdown of Tbxt exacerbated senescence and apoptosis in the H2O2-induced NPCs degeneration model. Conversely, upregulation of Tbxt alleviated these effects induced by H2O2. Mechanistically, bioinformatic analysis revealed that the direct downstream target genes of Tbxt were highly enriched in autophagy-related pathways and overexpression of Tbxt significantly activated autophagy in NPCs. Moreover, the administration of the autophagy inhibitor, 3-methyladenine, impeded the impact of Tbxt on the processes of senescence and apoptosis in NPCs. Further investigation revealed that Tbxt enhances autophagy by facilitating the transcription of ATG7 through its interaction with a specific motif within the promoter region. In conclusion, this study suggests that Tbxt mitigates H2O2-induced senescence and apoptosis of NPCs by activating ATG7-mediated autophagy.
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