PXD049800-1

PXD049800 is an original dataset announced via ProteomeXchange.

Title	Matrix-mediated activation of fibroblasts in rheumatoid arthritis
Description	Rheumatoid arthritis (RA) is an inflammatory autoimmune disease affecting synovial joints and leading to cartilage damage and bone loss. This destruction is promoted by activated fibroblast-like synoviocytes (FLS) that show an invasive and migratory phenotype. The mechanisms of FLS activation are unknown, but evidence suggests that pre-damaged extracellular matrix (ECM) of the cartilage can trigger FLS activation. Integrin α11β1 might be involved in the activation, as it is highly increased in the synovium of RA patients and hTNFtg mice, an RA mouse model. Since TNFα is the major cytokine induced in RA, we treated murine chondrocytes with TNFα to produce a damaged, RA-like matrix. Comparison to healthy chondrocyte matrix revealed decreased ECM proteins, including several collagens and proteoglycans, increased matrix-degrading proteins and elevated levels of inflammatory cytokines. FLS responded to those differences in the damaged chondrocyte matrix with a matrix-remodeling and pro-inflammatory phenotype characterized by expressing genes involved in matrix degradation and increased production of CLL11 and CCL19. Damaged chondrocyte matrix induced increased Itga11 expression in FLS, which correlates with the increased α11β1 amounts in RA patients. FLS deficient in integrin α11β1 released lower amounts of inflammation-associated cytokines but did not reveal significant differences from the response of wild type FLS to a damaged, RA-like matrix. Our results demonstrate differences in healthy and RA-like chondrocyte ECM and distinctly different responses of wt FLS to damaged versus healthy ECM.
HostingRepository	PRIDE
AnnounceDate	2025-01-14
AnnouncementXML	Submission_2025-01-14_00:33:36.851.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Luisa Marie Schmidt
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Eclipse

Revision	Datetime	Status	ChangeLog Entry
0	2024-02-20 04:04:45	ID requested
⏵ 1	2025-01-14 00:33:37	announced

10.1016/j.yexcr.2025.114408;

Zeinert I, Schmidt L, Baar T, Gatto G, De Giuseppe A, Korb-Pap A, Pap T, Mahabir E, Zaucke F, Brachvogel B, Kr, ü, ger M, Krieg T, Eckes B, Matrix-mediated activation of murine fibroblast-like synoviocytes. Exp Cell Res, 445(1):114408(2025) [pubmed]

submitter keyword: chondrocytes, cytokines, fibroblast-like synoviocytes,extracellular matrix

Beate Eckes
contact affiliation	Translational Matrix Biology, University of Cologne, Medical Faculty, Cologne, Germany
contact email	beate.eckes@uni-koeln.de
lab head
Luisa Marie Schmidt
contact affiliation	Novo Nordisk Foundation Center for Protein Research, University of Copenhagen
contact email	luisa.schmidt@cpr.ku.dk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD049800
     1. Label: PRIDE project
     2. Name: Matrix-mediated activation of fibroblasts in rheumatoid arthritis