METTL3 obstructs vascular smooth muscle cells osteogenic reprogramming by methylating Runx2 in chronic kidney disease.

ABSTRACT: The reprogrammed osteogenic phenotype of vascular smooth muscle cells (VSMCs) is considered a critical mechanism of vascular calcification (VC) in chronic kidney disease (CKD). Currently, the RNA N6-methyladenosine (m6A) modification is deciphered to be dynamically and reversibly participated in functional regulation of VSMCs. Here, we discover that serum m6A levels in RNA are dramatically reduced as VC progressed in patients with CKD, and this m6A demethylation is mainly due to the downregulation of methyltransferaselike-3 (METTL3). Functionally, METTL3 depletion exacerbates, whereas its overexpression attenuates calcification progression and osteogenic reprogramming. Mechanistically, Runx2, a crucial osteogenic gene, is identified as a key downstream target of METTL3-mediated m6A methyla

SUBMITTER: Cheng M 

PROVIDER: S-EPMC11978862 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature