PXD053766

PXD053766 is an original dataset announced via ProteomeXchange.

Title	Fibroblast-derived osteoglycin promotes epithelial cell repair
Description	There is an increasing need for pharmacological treatments that target defective epithelial repair in chronic diseases, such as chronic obstructive pulmonary disease. The mesenchymal niche plays a major regulatory role in guiding epithelial progenitor cell activation during repair. We persuaded that the secreted factors involved in this interaction hold potential as drug targets. In this study, we utilized a proteomics-guided drug discovery strategy, leveraging the secretome of lung fibroblasts, aimed to uncover drug targets affecting epithelial progenitor behavior. Using lung organoids, we identified several ligands with regenerative potential. Surprisingly, the matrix protein osteoglycin (OGN) had the most profound effect. RNA sequencing revealed that OGN promoted alveolar epithelial type II cell differentiation, whilst increasing reactive oxygen species detoxification, reducing senescence, and enhancing growth factor-mediated fibroblast-epithelial crosstalk. The idea that OGN protein plays a role in COPD was further substantiated by the finding that the expression was reduced in lung tissue of COPD patients and in smoke-exposed mice. Additionally, we found an active fragment of OGN comprising the leucine-rich repeat regions 4-7 to have comparable regenerative potential in regulating lung organoid formation. The active fragment of OGN ameliorated elastase-induced lung injury in murine precision-cut lung slices (PCLS) and improved lung function in mice. These findings identify lung fibroblast-derived OGN as a matrix protein supporting alveolar epithelial growth and its active fragment as a promising therapeutic target for epithelial cell repair in individuals with accelerated tissue damage.
HostingRepository	PRIDE
AnnounceDate	2025-04-15
AnnouncementXML	Submission_2025-04-15_00:14:48.568.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Justina Clarinda Wolters
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2024-07-08 10:00:54	ID requested
⏵ 1	2025-04-15 00:14:49	announced

10.1038/s41536-025-00404-3;

van der Koog L, Woest ME, Gorter IC, Verschut V, Elferink RAB, Zuidhof AB, Nugraha DF, Koloko Ngassie ML, Bos SIT, Dhakad D, Wolters JC, Horvatovich PL, Prakash YS, Timens W, Yildirim Ö A, Brandsma CA, Frijlink HW, Nagelkerke A, Gosens R, Fibroblast-derived osteoglycin promotes epithelial cell repair. NPJ Regen Med, 10(1):16(2025) [pubmed]

submitter keyword: proteomics, epithial cells, ostyglycin,COPD

Dr. J.C.Wolters
contact affiliation	Department of Pediatrics, UMCG/RUG, Groningen, The Netherlands
contact email	j.c.wolters@umcg.nl
lab head
Justina Clarinda Wolters
contact affiliation	UMCG
contact email	j.c.wolters@umcg.nl
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/2025/04/PXD053766

PRIDE project URI

• PRIDE
  1. PXD053766
     1. Label: PRIDE project
     2. Name: Fibroblast-derived osteoglycin promotes epithelial cell repair