The m⁶A methyltransferase Mettl3 deficiency attenuates hepatic stellate cell activation and liver fibrosis.

ABSTRACT: Activation of hepatic stellate cells (HSCs) is a central driver of liver fibrosis. Previous investigations have identified various altered epigenetic landscapes during the cellular progression of HSC activation. N6-methyladenosine (m⁶A) is the most abundant internal RNA modification in eukaryotic cells and is dynamically regulated under various physiological and pathophysiological conditions. However, the functional role of Mettl3-mediated m⁶A in liver fibrosis remains elusive. Here, we found that the HSC-specific knockout of m⁶A methyltransferase Mettl3 suppressed HSC activation and significantly alleviated liver fibrosis. Multi-omics analysis of HSCs showed that Mettl3 depletion reduced m⁶A deposition on mRNA transcripts of Lats2 (a central pla

SUBMITTER: Li Y 

PROVIDER: S-EPMC9734030 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature