METTL3-mediated macrophage exosomal NEAT1 contributes to hepatic fibrosis progression through Sp1/TGF-β1/Smad signaling pathway.

ABSTRACT: Hepatic fibrosis (HF) is caused by chronic hepatic injury and is characterized by hepatic stellate cells (HSCs) activation. Studies focusing on the function of exosomes derived from macrophages in HF progression are limited. This study aims to identify the roles of exosomal NEAT1 derived from macrophages on HF and the underlying mechanisms. Our studies showed that METTL3 targeted and enhanced NEAT1 expression in macrophages. Exosomal NEAT1 originating from LPS-treated macrophages promoted HSCs proliferation and migration, and induced the expression of fibrotic proteins including collagen I, α-SMA, and fibronectin. Macrophage exosomal NEAT1 contributed to HSCs activation by sponging miR-342. MiR-342 directly targeted Sp1 and suppressed its downstream TGF-β1/Smad signaling pathway, which eve

SUBMITTER: Shu B 

PROVIDER: S-EPMC9117676 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature