KMT2A regulates the autophagy-GATA4 axis through METTL3-mediated m⁶A modification of ATG4a to promote NPCs senescence and IVDD progression.

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

SUBMITTER: Wu O 

PROVIDER: S-EPMC11582572 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature