PXD071531

PXD071531 is an original dataset announced via ProteomeXchange.

Title	Methionine Restriction Alleviates Kidney Fibrosis through Epigenetic Repression of the TGF-β-Smad3-Hoxc8/P-TEFb axis
Description	Low-protein diets can mitigate renal fibrosis, yet the critical amino acid responsible for this benefit and its underlying mechanism remain unclear. By screening 15 amino acid–restricted diets in a unilateral ureteral obstruction (UUO) model, we identify methionine restriction (MetR) as the most effective intervention. Integrating transcriptomic and cistromic analyses further uncover Hoxc8 as a central pro-fibrotic transcription factor. Hoxc8 is induced by TGF-β–Smad3, amplifies its own expression, and drives fibrotic gene programs through recruitment of the P-TEFb transcriptional elongation complex. Clinically, HOXC8 is elevated in fibrotic human kidneys, and fibroblast-specific Hoxc8 deletion protects mice from fibrosis. MetR attenuates this pro-fibrotic circuit by reducing active histone marks (H3K4me3 and H3K36me3) at the Hoxc8 locus, thereby suppressing the Hoxc8-dependent fibrotic transcriptional program. Together, these findings establish the TGF-β–Smad3–Hoxc8/P-TEFb axis as a key driver of renal fibrosis and highlight MetR as a promising therapeutic strategy.
HostingRepository	PRIDE
AnnounceDate	2025-12-04
AnnouncementXML	Submission_2025-12-03_21:25:25.711.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Yunjing Liu
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2025-12-03 06:14:02	ID requested
⏵ 1	2025-12-03 21:25:26	announced

Dataset with its publication pending

submitter keyword: kidney fibrosis

methionine restriction

Hoxc8

P-TEFb

Yunjing Liu
contact affiliation	The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China
contact email	15626441459@163.com
lab head
Yunjing Liu
contact affiliation	Tianjin Medical University
contact email	15626441459@163.com
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/2025/12/PXD071531

PRIDE project URI

• PRIDE
  1. PXD071531
     1. Label: PRIDE project
     2. Name: Methionine Restriction Alleviates Kidney Fibrosis through Epigenetic Repression of the TGF-β-Smad3-Hoxc8/P-TEFb axis