KMT2A regulates the autophagy-GATA4 axis through METTL3-mediated m

Ouqiang Wu, Yuxin Jin, Zhiguang Zhang, Hao Zhou, Wenbin Xu, Linjie Chen, Morgan Jones, Kenny Yat Hong Kwan, Jianyuan Gao, Kai Zhang, Xiaofei Cheng, Qizhu Chen, Xinzhou Wang, Yan Michael Li, Zhenyu Guo, Jing Sun, Zhihua Chen, Bin Wang, Xiangyang Wang, Shuying Shen, Aimin Wu

Department of Orthopaedics, Key Laboratory of Structural Malformations in Children of Zhejiang Province, Key Laboratory of Orthopaedics of Zhejiang Province, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China. · pubmed

Paper

Abstract

Intervertebral disc degeneration (IVDD), a disease associated with ageing, is characterised by a notable increase in senescent nucleus pulposus cells (NPCs) as IVDD progresses. However, the specific mechanisms that regulate the senescence of NPCs remain unknown. In this study, we observed impaired autophagy in IVDD-NPCs, which contributed to the upregulation of NPCs senescence and the senescence-associated secretory phenotype (SASP). The dysregulated SASP disrupted NPCs viability and initiated extracellular matrix degradation. Conversely, the restoration of autophagy reversed the senescence phenotype by inhibiting GATA binding protein 4 (GATA4). Moreover, we made the novel observation that a cross-talk between histone H3 lysine 4 trimethylation (H3K4me3) modification and N6-methyladenosine(m

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Research summary

The paper addresses the mechanisms of intervertebral disc degeneration (IVDD) and the role of autophagy in regulating senescence in nucleus pulposus cells, which is relevant to aging and age-related degeneration. However, while it contributes to understanding the biological processes involved, it primarily focuses on a specific disease mechanism rather than addressing broader root causes of aging or lifespan extension. Thus, its impact is solid but limited.

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