自噬
昼夜节律
细胞生物学
生物
转录组
椎间盘
转录因子
生物钟
机制(生物学)
变性(医学)
小RNA
基因
神经科学
遗传学
医学
解剖
病理
基因表达
认识论
哲学
细胞凋亡
作者
Liangwei Mei,Yi Zheng,Xue Gao,Teng Ma,Bing Xia,Yiming Hao,Bin Wei,Yitao Wei,Zhuojing Luo,Jinghui Huang
标识
DOI:10.1016/j.phrs.2022.106537
摘要
The intervertebral disc has an intrinsic circadian rhythm, elimination of which leads to stress in nucleus pulposus cells (NPCs), contributing to intervertebral disc degeneration (IDD). Disruption or deletion of Bmal1 (a core transcription factor) results in complete loss of circadian rhythms, make mice susceptibility to IDD. However, the underlying mechanism by which Bmal1 mediates IDD is remains enigmatic, and whether there are other upstream factors regulating Bmal1 in NPCs. In our study, we first found that the decrease of Bmal1 was significantly correlated with the grades of IDD. With gain- and loss-of-function, Bmal1 shown a protective effect on NPC viability and functions. Transcriptomic and proteomic landscape reveals the functional contributions of Bmal1, and phosphoproteomic analysis links to autophagy. Bioinformatics analysis identified that a novel miRNA hsa-let-7f-1-3p was directly target Bmal1 3'UTR and negatively correlated with NPC function. Finally, our animal model confirmed the protective role of Bmal1 in rat IDD and this effect could be attenuated by hsa-let-7f-1-3p. The hsa-let-7f-1-3p/Bmal1/autophagy axis provides a potential therapeutic strategy for the clinical treatment of IDD.
科研通智能强力驱动
Strongly Powered by AbleSci AI