PXD011134

PXD011134 is an original dataset announced via ProteomeXchange.

Title	TGF-β1/p65/MAT2A: a novel pathway involved in the regulation of intracellular SAM and liver fibrogenesis - Part1
Description	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.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:15:11.328.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Qian Liu
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2018-09-18 06:27:36	ID requested
1	2019-11-12 14:15:24	announced
⏵ 2	2024-10-22 04:15:13	announced	2024-10-22: Updated project metadata.

10.1016/j.ebiom.2019.03.058;

Wang K, Fang S, Liu Q, Gao J, Wang X, Zhu H, Zhu Z, Ji F, Wu J, Ma Y, Hu L, Shen X, Gao D, Zhu J, Liu P, Zhou H, 1/p65/MAT2A pathway regulates liver fibrogenesis via intracellular SAM. EBioMedicine, 42():458-469(2019) [pubmed]

submitter keyword: proteomics;liver fibrosis

MAT2A

Hu Zhou
contact affiliation	SIMM
contact email	zhouhu@simm.ac.cn
lab head
Qian Liu
contact affiliation	Shanghai Institute of Materia Medica
contact email	liuqian_scu@163.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD011134
     1. Label: PRIDE project
     2. Name: TGF-β1/p65/MAT2A: a novel pathway involved in the regulation of intracellular SAM and liver fibrogenesis - Part1