PXD047924-2

PXD047924 is an original dataset announced via ProteomeXchange.

Title	Natural small molecule DP combats liver fibrosis by targeting APOL2
Description	Liver fibrosis is an urgent clinical problem without effective treatment. Herein, we conducted a high-content screening on a natural “privileged” diterpenoid library to identify a potent anti-liver fibrosis lead DP. Leveraging photoaffinity labeling approach, apolipoprotein L2 (APOL2), an ER-rich protein, was identified as the direct target of DP. APOL2 is mainly expressed in activated hepatic stellate cells (HSCs) and could activate HSCs to synthesize ECM proteins. It can be induced by TGF-β1 and be antagonized by DP. Mechanistically, upon TGF-β1stimulation, APOL2 binds ER Ca2+ pump SERCA2 to trigger ER stress, elevating its downstream PERK-HES1 axis to promote liver fibrosis, mildly dependent on the canonical TGF-β/Smad signaling. As a result, ablation of APOL2 significantly alleviated TGF-β1-stimulated HSCs activation, and abolished anti-fibrosis effect of DP. Our findings not only define APOL2 as a novel therapeutic target for liver fibrosis, but also highlight DP as a promising lead for treatment of this symptom.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:54:48.153.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Lu Gan
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2023-12-18 19:52:41	ID requested
1	2024-08-13 03:12:23	announced
⏵ 2	2024-10-22 06:54:48	announced	2024-10-22: Updated project metadata.

Gan L, Jiang Q, Huang D, Wu X, Zhu X, Wang L, Xie W, Huang J, Fan R, Jing Y, Tang G, Li XD, Guo J, Yin S, A natural small molecule alleviates liver fibrosis by targeting apolipoprotein L2. Nat Chem Biol, 21(1):80-90(2025) [pubmed]

10.1038/s41589-024-01704-3;

submitter keyword: APOL2, Anti-liver fibrosis,Natural small molecule, ER stress, HES1

Sheng Yin
contact affiliation	School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, Guangdong, P.R. China.
contact email	yinsh2@mail.sysu.edu.cn
lab head
Lu Gan
contact affiliation	School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, Guangdong, P.R. China.
contact email	ganlu27@mail2.sysu.edu.cn
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/08/PXD047924

PRIDE project URI

• PRIDE
  1. PXD047924
     1. Label: PRIDE project
     2. Name: Natural small molecule DP combats liver fibrosis by targeting APOL2