PXD011135 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | TGF-β1/p65/MAT2A: a novel pathway involved in the regulation of intracellular SAM and liver fibrogenesis - Part2 |
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 | 2019-11-12 |
AnnouncementXML | Submission_2019-11-12_14:28:03.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 | No PTMs are included in the dataset |
Instrument | TSQ Quantiva |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2018-09-18 06:27:46 | ID requested | |
⏵ 1 | 2019-11-12 14:28:05 | announced | |
Publication List
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] |
Keyword List
submitter keyword: proteomics;liver fibrosis;MAT2A |
Contact List
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 | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD011135
- Label: PRIDE project
- Name: TGF-β1/p65/MAT2A: a novel pathway involved in the regulation of intracellular SAM and liver fibrogenesis - Part2