PXD068544

PXD068544 is an original dataset announced via ProteomeXchange.

Title	SETDB1-Dependent Modulation of the TGFb-induced Secretome in Duchenne Muscular Dystrophy: The Role of EMILIN1
Description	Duchenne Muscular Dystrophy (DMD) is a severe X-linked muscle-wasting disorder characterized by chronic inflammation, progressive fibrosis, and impaired muscle regeneration. The TGFb pathway is overactivated in DMD and it sustains the accumulation of extracellular matrix (ECM), contributing to fibrosis. Our previous results showed that SETDB1 regulates the expression of TGFb-dependent secreted factors impacting fibrosis and myogenic differentiation. In particular, the conditioned medium (CM) of TGFb-treated myotubes impairs myoblasts differentiation and increase fibrosis. In this study, we performed a thorough proteomic analysis of the secretome from DMD myotubes under TGFb stimulation, with or without SETDB1 LOF, to identify secreted factors involved in the dysregulated regenerative environment of DMD. We found that SETDB1 modulates the TGFb-induced secretome, particularly by regulating ECM-related proteins. Among these, we identified EMILIN1, an ECM glycoprotein not previously studied in skeletal muscle. EMILIN1 is upregulated by TGFb reduced upon SETDB1 depletion and more abundant in DMD myotubes. Functional analyses revealed that EMILIN1 LOF impairs late myogenic differentiation and reduces the expression of the fibrotic marker SERPINE1. These findings highlight EMILIN1 as a secreted regulator of myogenesis and fibrosis, and support the role of SETDB1 in regulating the TGFb-dependent secretome in DMD. This study provides new insights into the molecular players contributing to the fibrotic and regenerative defects in DMD, offering potential therapeutic targets for disease intervention.
HostingRepository	PRIDE
AnnounceDate	2026-08-24
AnnouncementXML	Submission_2026-08-23_16:46:52.691.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Guillaume CHEVREUX
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	L-cysteine methyl disulfide; phosphorylated residue; monohydroxylated residue; deamidated residue
Instrument	timsTOF Pro 2

Revision	Datetime	Status	ChangeLog Entry
0	2025-09-19 02:08:29	ID requested
⏵ 1	2026-08-23 16:46:53	announced

10.1038/s41419-026-08825-8;

Zamperoni M, Muraine L, Tran MY, Granados A, Bigot A, Petit V, Bensalah M, Ohana J, Legros V, Boyarchuk E, Bruce J, Chevreux G, Joliot V, Negroni E, Moulin M, Trollet C, Ait-Si-Ali S, /SETDB1-regulated secreted biomarker in Duchenne muscular dystrophy. Cell Death Dis, 17(1):(2026) [pubmed]

submitter keyword: EMILIN1,DMD, SETDB1, TGF, secretome, myotube

Slimane Ait-Si-Ali
contact affiliation	Université Paris Cité, CNRS, Epigenetics and Cell Fate, UMR7216, F-75013 Paris, France
contact email	slimane.aitsiali@u-paris.fr
lab head
Guillaume CHEVREUX
contact affiliation	Institut Jacques Monod, CNRS UMR7592
contact email	guillaume.chevreux@ijm.fr
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD068544
     1. Label: PRIDE project
     2. Name: SETDB1-Dependent Modulation of the TGFb-induced Secretome in Duchenne Muscular Dystrophy: The Role of EMILIN1