Prostaglandin E2 (PGE2) and Roflumilast Involvement in IPF Progression.
IPF
PGE2
Roflumilast
extracellular matrix
fibroblast
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
03 Aug 2023
03 Aug 2023
Historique:
received:
29
06
2023
revised:
31
07
2023
accepted:
03
08
2023
medline:
14
8
2023
pubmed:
12
8
2023
entrez:
12
8
2023
Statut:
epublish
Résumé
The ECM propagates processes in idiopathic pulmonary fibrosis (IPF), leading to progressive lung scarring. We established an IPF-conditioned matrix (IPF-CM) system as a platform for testing drug candidates. Here, we tested the involvement of a PGE2 and PDE4 inhibitor, Roflumilast, in the IPF-CM system. Primary normal/IPF tissue-derived human lung fibroblasts (N/IPF-HLFs) were cultured on Matrigel and then removed to create the IPF-CM. N-HLFs were exposed to the IPF-CM/N-CM with/without PGE2 (1 nM) and Roflumilast (1 µM) for 24 h. The effect of the IPF-CM on cell phenotype and pro-fibrotic gene expression was tested. In addition, electronic records of 107 patients with up to 15-year follow-up were retrospectively reviewed. Patients were defined as slow/rapid progressors using forced vital capacity (FVC) annual decline. Medication exposure was examined. N-HLFs cultured on IPF-CM were arranged in large aggregates as a result of increased proliferation, migration and differentiation. A PGE2 and Roflumilast combination blocked the large aggregate formation induced by the IPF-CM (
Identifiants
pubmed: 37569768
pii: ijms241512393
doi: 10.3390/ijms241512393
pmc: PMC10418473
pii:
doi:
Substances chimiques
Dinoprostone
K7Q1JQR04M
Roflumilast
0P6C6ZOP5U
Types de publication
Review
Journal Article
Langues
eng
Sous-ensembles de citation
IM
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