TGF-β1/p65/MAT2A pathway regulates liver fibrogenesis via intracellular SAM.

ABSTRACT:

Background

Hepatic stellate cell (HSC) activation induced by transforming growth factor β1 (TGF-β1) plays a pivotal role in fibrogenesis, while the complex downstream mediators of TGF-β1 in such process are largely unknown.

Methods

We performed pharmacoproteomic profiling of the mice liver tissues from control, carbon tetrachloride (CCl₄)-induced fibrosis and NPLC0393 administrated groups. The target gene MAT2A was overexpressed or knocked down in vivo by tail vein injection of AAV vectors. We examined NF-κB transcriptional activity on MAT2A promoter via luciferase assay. Intracellular SAM contents were analyzed by LC-MS method.

Findings

We found that methionine adenosyltransferase 2A (MAT2A) is significantly upregulated in the CCl₄-induced fibro

SUBMITTER: Wang K 

PROVIDER: S-EPMC6491716 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature