Dataset Information

Fibroblast-derived osteoglycin promotes epithelial cell repair

ABSTRACT: 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.

INSTRUMENT(S): Orbitrap Exploris 480

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell

DISEASE(S): Chronic Obstructive Pulmonary Disease

SUBMITTER: Justina Clarinda Wolters

LAB HEAD: Dr. J.C.Wolters

PROVIDER: PXD053766 | Pride | 2025-04-15

REPOSITORIES: Pride

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Dataset's files

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			Action	DRS
	2021-36_2021-42_SN16withHELAlib_MS2Quant_Qclassic_LocalNorm_NoImp.xlsx	Xlsx
	2021-36_EV1.raw	Raw
	2021-36_SF1.raw	Raw
	2021-36_SF2.raw	Raw
	2021-36_SF3.raw	Raw

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Fibroblast-derived osteoglycin promotes epithelial cell repair.

van der Koog Luke L Woest Manon E ME Gorter Iris C IC Verschut Vicky V Elferink Robin A B RAB Zuidhof Annet B AB Nugraha Dyan F DF Koloko Ngassie Maunick L ML Bos Sophie I T SIT Dhakad Deepesh D Wolters Justina C JC Horvatovich Peter L PL Prakash Y S YS Timens Wim W Yildirim Önder A ÖA Brandsma Corry-Anke CA Frijlink Henderik W HW Nagelkerke Anika A Gosens Reinoud R

NPJ Regenerative medicine 20250325 1

There is an urgent need for innovative therapies targeting defective epithelial repair in chronic diseases like COPD. The mesenchymal niche is a critical regulator in epithelial stem cell activation, suggesting that their secreted factors are possible potent drug targets. Utilizing a proteomics-guided drug discovery strategy, we explored the lung fibroblast secretome to uncover impactful drug targets. Our lung organoid assays identified several regenerative ligands, with osteoglycin (OGN) showin ...[more]

PMID: 40133363

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