Prostaglandin E2 (PGE2) and Roflumilast Involvement in IPF Progression
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 syst...
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| Format: | Article |
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MDPI AG
2023-08-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/15/12393 |
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| author | Noa Moshkovitz Gali Epstein Shochet David Shitrit |
| author_facet | Noa Moshkovitz Gali Epstein Shochet David Shitrit |
| author_sort | Noa Moshkovitz |
| collection | DOAJ |
| description | 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 (<i>p</i> < 0.001) as well as cell migration, proliferation, and pro-fibrotic gene expression. A review of patient records showed that significantly more slow-progressing patients were exposed to NSAIDs (<i>p</i> = 0.003). PGE2/PDE4 signaling may be involved in IPF progression. These findings should be further studied. |
| first_indexed | 2024-03-11T00:25:22Z |
| format | Article |
| id | doaj.art-567b92c41e2a4db09d461733aab79cba |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T00:25:22Z |
| publishDate | 2023-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-567b92c41e2a4db09d461733aab79cba2023-11-18T23:04:26ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-08-0124151239310.3390/ijms241512393Prostaglandin E2 (PGE2) and Roflumilast Involvement in IPF ProgressionNoa Moshkovitz0Gali Epstein Shochet1David Shitrit2Pulmonary Department, Meir Medical Center, Kfar Saba 44281, IsraelPulmonary Department, Meir Medical Center, Kfar Saba 44281, IsraelPulmonary Department, Meir Medical Center, Kfar Saba 44281, IsraelThe 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 (<i>p</i> < 0.001) as well as cell migration, proliferation, and pro-fibrotic gene expression. A review of patient records showed that significantly more slow-progressing patients were exposed to NSAIDs (<i>p</i> = 0.003). PGE2/PDE4 signaling may be involved in IPF progression. These findings should be further studied.https://www.mdpi.com/1422-0067/24/15/12393IPFPGE2Roflumilastextracellular matrixfibroblast |
| spellingShingle | Noa Moshkovitz Gali Epstein Shochet David Shitrit Prostaglandin E2 (PGE2) and Roflumilast Involvement in IPF Progression International Journal of Molecular Sciences IPF PGE2 Roflumilast extracellular matrix fibroblast |
| title | Prostaglandin E2 (PGE2) and Roflumilast Involvement in IPF Progression |
| title_full | Prostaglandin E2 (PGE2) and Roflumilast Involvement in IPF Progression |
| title_fullStr | Prostaglandin E2 (PGE2) and Roflumilast Involvement in IPF Progression |
| title_full_unstemmed | Prostaglandin E2 (PGE2) and Roflumilast Involvement in IPF Progression |
| title_short | Prostaglandin E2 (PGE2) and Roflumilast Involvement in IPF Progression |
| title_sort | prostaglandin e2 pge2 and roflumilast involvement in ipf progression |
| topic | IPF PGE2 Roflumilast extracellular matrix fibroblast |
| url | https://www.mdpi.com/1422-0067/24/15/12393 |
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