Fibroblasts are not just fibroblasts: clear differences between dermal and pulmonary fibroblasts' response to fibrotic growth factors.


Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
09 06 2023
Historique:
received: 20 02 2023
accepted: 03 06 2023
medline: 12 6 2023
pubmed: 10 6 2023
entrez: 9 6 2023
Statut: epublish

Résumé

Systemic Sclerosis (SSc) hallmark is skin fibrosis, but up to 80% of the patients have fibrotic involvement in the pulmonary system. Antifibrotic drugs which have failed in a general SSc population have now been approved in patients with SSc-associated interstitial lung disease (ILD). This indicates that the fibrotic progression and regulation of fibroblasts likely depend on local factors specific to the tissue type. This study investigated the difference between dermal and pulmonary fibroblasts in a fibrotic setting, mimicking the extracellular matrix. Primary healthy fibroblasts were grown in a crowded environment and stimulated with TGF-β1 and PDGF-AB. The viability, morphology, migration capacity, extracellular matrix formation, and gene expression were assessed: TGF-β1 only increased the viability in the dermal fibroblasts. PDGF-AB increased the migration capacity of dermal fibroblasts while the pulmonary fibroblasts fully migrated. The morphology of the fibroblasts was different without stimulation. TGF-β1 increased the formation of type III collagen in pulmonary fibroblasts, while PDGF-AB increased it in dermal fibroblasts. The gene expression trend of type VI collagen was the opposite after PDGF-AB stimulation. The fibroblasts exhibit different response profiles to TGF-β1 and PDGF-AB; this suggests that drivers of fibrosis are tissue-dependent, which needs to be considered in drug development.

Identifiants

pubmed: 37296166
doi: 10.1038/s41598-023-36416-6
pii: 10.1038/s41598-023-36416-6
pmc: PMC10256773
doi:

Substances chimiques

Transforming Growth Factor beta1 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

9411

Informations de copyright

© 2023. The Author(s).

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Auteurs

Sofie Falkenløve Madsen (SF)

Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark. som@nordicbio.com.
Immunoscience, Nordic Bioscience, Herlev, Denmark. som@nordicbio.com.

Jannie Marie Bülow Sand (JMB)

Hepatic and Pulmonary Research, Nordic Bioscience, Herlev, Denmark.

Pernille Juhl (P)

Immunoscience, Nordic Bioscience, Herlev, Denmark.

Morten Karsdal (M)

Immunoscience, Nordic Bioscience, Herlev, Denmark.

Christian S Thudium (CS)

Immunoscience, Nordic Bioscience, Herlev, Denmark.

Anne Sofie Siebuhr (AS)

Immunoscience, Nordic Bioscience, Herlev, Denmark.

Anne-Christine Bay-Jensen (AC)

Immunoscience, Nordic Bioscience, Herlev, Denmark.

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