PXD069194-1

PXD069194 is an original dataset announced via ProteomeXchange.

Title	Inhibition of a matrisomal TGFβ hub does not reduce collagen synthesis by Dupuytren’s fibroblasts C4PR_LIV
Description	Dupuytren’s disease is a fibroproliferative disorder of the palmer fascia characterized by flexion contractures in the hand. Dupuytren’s can be treated surgically but disease recurrence rates are high, potentially due to a continual production of matrisomal proteins. Here, metabolic labelling and proteomics were used to determine the differences in the new synthesis and composition of matrisomal proteins between Dupuytren’s tissue and normal palmar fascia. Dupuytren’s tissue actively synthesised type I collagen, fibronectin, matrix metalloproteinases-2 and -3 (MMP2, MMP3) and Tissue Inhibitor of Metalloproteinases 2 (TIMP2). Both tissues actively synthesized Insulin-Like Growth Factor Binding Protein 7 (IGFBP7). Label-free analysis implicated the TGFβ pathway in the matrisomal profile of Dupuytren’s tissue. The effect of TGFβ on COL1 gene expression was first tested in cultured young and old equine tenocytes. COL1A1 was particularly responsive to TGFβ treatment and was more highly expressed in cells from old samples. In old human cells, COL1A1 and COL1A2 expression was higher in cells derived from Dupuytren's tissue than normal palmar fascia and in response to TGFβ1, but no changes in COL1A1 or COL1A2 CpG methylation were detected. TGFβ1 treatment only resulted in increased type I collagen protein accumulation in the media of Dupuytren’s nodule cells. In 3D cultures, COL1A1 expression was lower in normal palmar fascia than in Dupuytren’s cells but TGFβ1 treatment only increased type I collagen accumulation in media of normal palmar fascia cultures, and TGFβ1 inhibition did not alter new collagen protein synthesis. TGFβ1 inhibition in Dupuytren’s tissue explants did not alter the proportion of homotrimeric type I collagen, nor was this changed in skin or tendon of the tight-skin (TSK) mouse, a naturally occurring model of indirect TGFβ1 activation. The role of TGFβ in Dupuytren's disease may be predominantly related to myofibroblast phenoconversion and contractility rather than directly altering collagen protein synthesis.
HostingRepository	PRIDE
AnnounceDate	2026-03-16
AnnouncementXML	Submission_2026-03-16_04:20:23.183.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD069194
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Philip Brownridge
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2025-10-08 02:21:58	ID requested
⏵ 1	2026-03-16 04:20:24	announced
2	2026-03-17 07:21:25	announced	2026-03-17: Updated project metadata.

Cooper G, Gumbs JA, Alkharabsheh S, Lee KJ, Carter A, Coleman H, O'Heneghan-Yates NS, Ijaz R, Beamish E, Menezes LA, Liloglou T, Clegg PD, Canty-Laird EG, 1 signalling from collagen protein synthesis in Dupuytren's disease. J Pathol, 268(4):383-397(2026) [pubmed]

10.1002/path.70020;

10.6019/PXD069194;

submitter keyword: Dupuytren’s disease, fibroblasts

Dr Elizabeth Laird
contact affiliation	Department of Musculoskeletal and Ageing Science Institute of Life Course and Medical Sciences University of Liverpool, UK
contact email	eglaird@liverpool.ac.uk
lab head
Philip Brownridge
contact affiliation	University of Liverpool
contact email	philipjb@liv.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD069194
     1. Label: PRIDE project
     2. Name: Inhibition of a matrisomal TGFβ hub does not reduce collagen synthesis by Dupuytren’s fibroblasts C4PR_LIV