Targeting the m⁶A RNA methyltransferase METTL3 attenuates the development of kidney fibrosis.

ABSTRACT: Kidney fibrosis is a major mechanism underlying chronic kidney disease (CKD). N⁶-methyladenosine (m⁶A) RNA methylation is associated with organ fibrosis. We investigated m⁶A profile alterations and the inhibitory effect of RNA methylation in kidney fibrosis in vitro (TGF-β-treated HK-2 cells) and in vivo (unilateral ureteral obstruction [UUO] mouse model). METTL3-mediated signaling was inhibited using siRNA in vitro or the METTL3-specific inhibitor STM2457 in vivo and in vitro. In HK-2 cells, METTL3 protein levels increased in a dose- and time-dependent manner along with an increase in the cellular m⁶A levels. In the UUO model, METTL3 expression and m⁶A levels were significantly increased. Transcriptomic and m⁶A profiling de

SUBMITTER: Jung HR 

PROVIDER: S-EPMC10907702 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature