PXD046296

PXD046296 is an original dataset announced via ProteomeXchange.

Title	TMEM43 as a Promising Target for Ameliorating Organ Fibrosis and Identification of two FDA-approved Anti-fibrosis Drugs
Description	Fibrosis, characterized by the abnormal deposition of extracellular matrix, can cause organ dysfunction and mortality. However, research on the mechanisms of fibrosis, especially that focusing on the identification of drug targets, is currently still lacking. This study is the first to reveal that a small molecule (YTB-8) derived from the natural β-carboline alkaloid flazin has potent protective effects against renal fibrosis in vitro and in vivo. The cellular target of YTB-8, a nuclear and endoplasmic reticulum membrane protein known as transmembrane protein 43 (TMEM43), was identified by activity-based protein profiling (ABPP) strategy in a renal fibrosis model. YTB-8 was found to interact with amino acids Arg312 and Leu382 of TMEM43 and exert anti-renal fibrosis effects by suppressing the NF-κB and TGF-β/Smad signaling pathways. Utilization of simulated TMEM43 and its pocket structure for virtual screening, followed by in vitro and in vivo detection, led to us identifying two FDA-approved drugs, drospirenone and adapalene, with anti-renal fibrosis efficacy. TMEM43 was also found to be the target of YTB-8 in its alleviation of lung, liver, and skin fibrosis in vitro, verifying the value of TMEM43 as a general target for new-generation drug design relating to organ fibrosis. Collectively, these findings revealed TMEM43 to be a promising universal cellular target for organ fibrosis intervention.
HostingRepository	iProX
AnnounceDate	2023-10-20
AnnouncementXML	Submission_2023-10-22_19:18:07.916.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jijun Li
SpeciesList	scientific name: Rattus norvegicus; NCBI TaxID: 10116;
ModificationList	No PTMs are included in the dataset
Instrument	Thermo Scientific instrument model

Revision	Datetime	Status	ChangeLog Entry
0	2023-10-22 19:16:36	ID requested
⏵ 1	2023-10-22 19:18:08	announced

Dataset with its publication pending

submitter keyword: Fibrosis, β-carboline, TMEM43, inhibition, drug repurposing

Jianbing Jiang
contact affiliation	Institute for Inheritance-Based Innovation of Chinese Medicine, School of Pharmacy, Shenzhen University Medical School, Shenzhen University
contact email	jb.jiang@szu.edu.cn
lab head
Jijun Li
contact affiliation	Institute for Inheritance-Based Innovation of Chinese Medicine, School of Pharmacy, Shenzhen University Medical School, Shenzhen University
contact email	2350241010@email.szu.edu.cn
dataset submitter

iProX dataset URI