Proteomics

Dataset Information

0

TGF-β1/p65/MAT2A: a novel pathway involved in the regulation of intracellular SAM and liver fibrogenesis - Part1


ABSTRACT: Hepatic stellate cell (HSC) activation induced by transforming growth factor β (TGF-β1) plays a pivotal role in the fibrogenesis. The complex downstream mediators of TGF-β1 are largely unknown. Here, proteomics analysis and biological validation demonstrated that methionine adenosyltransferase 2A (MAT2A) was significantly upregulated in a CCl4-induced fibrosis mice model and a small molecule NPLC0393, known to block TGF-β1/Smad3 signaling, inhibited its upregulation. In HSC cells, TGF-β1 induced elevation of MAT2A and MAT2β expression as well as reduction of S-adenosylmethionine (SAM) content, which further promoted HSC activation. Functionally, in vivo and in vitro knockdown of MAT2A alleviated CCl4- and TGF-β1-induced HSC activation, whereas in vivo overexpression of MAT2A facilitated hepatic fibrosis and abolished therapeutic effect of NPLC0393. TGF-β1 induced p65 phosphorylation and NF-κB activation, thereby promoted the transcription of MAT2A and its protein expression. In addition, overexpression of p65 abrogated NPLC0393 mediated inhibition of HSC activation. This study identified a novel pathway TGF-β1/p65/MAT2A that was involved in the regulation of intracellular SAM contents and liver fibrogenesis, suggesting that this pathway is a potential therapeutic target for hepatic fibrosis.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Liver

SUBMITTER: Qian Liu  

LAB HEAD: Hu Zhou

PROVIDER: PXD011134 | Pride | 2019-11-12

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
20131031_WangKF_B1.raw Raw
20131031_WangKF_B2.raw Raw
20131031_WangKF_B3.raw Raw
20131031_WangKF_B4.raw Raw
20131031_WangKF_B5.raw Raw
Items per page:
1 - 5 of 20
altmetric image

Publications


<h4>Background</h4>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.<h4>Methods</h4>We performed pharmacoproteomic profiling of the mice liver tissues from control, carbon tetrachloride (CCl<sub>4</sub>)-induced fibrosis and NPLC0393 administrated groups. The target gene MAT2A was overexpressed or knocked down in vivo by tail vein inje  ...[more]

Similar Datasets

2019-11-12 | PXD011135 | Pride
2024-08-06 | PXD052806 | Pride
2021-09-09 | PXD019448 | Pride
2020-04-29 | GSE149508 | GEO
2015-02-19 | E-GEOD-52253 | biostudies-arrayexpress
2024-07-06 | GSE271355 | GEO
2024-07-06 | GSE271352 | GEO
2024-07-06 | GSE271354 | GEO
2020-12-01 | GSE161981 | GEO
2009-08-25 | E-GEOD-17518 | biostudies-arrayexpress