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2013-06-03

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cc by (c) Gabasa et al., 2013
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/126461

Lung Myofibroblasts Are Characterized by DownRegulated Cyclooxygenase-2 and Its Main Metabolite, Prostaglandin E2

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https://doi.org/10.1371/journal.pone.0065445

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Background: Prostaglandin E2 (PGE(2)), the main metabolite of cyclooxygenase (COX), is a well-known anti-fibrotic agent. Moreover, myofibroblasts expressing alpha-smooth muscle actin (alpha-SMA), fibroblast expansion and epithelial-mesenchymal transition (EMT) are critical to the pathogenesis of idiopathic pulmonary fibrosis (IPF). Our aim was to investigate the expression of COX-2 and PGE(2) in human lung myofibroblasts and establish whether fibroblast-myofibroblast transition (FMT) and EMT are associated with COX-2 and PGE(2) down-regulation. Methods: Fibroblasts obtained from IPF patients (n = 6) and patients undergoing spontaneous pneumothorax (control, n = 6) and alveolar epithelial cell line A549 were incubated with TGF-beta 1 and FMT and EMT markers were evaluated. COX-2 and alpha-SMA expression, PGE(2) secretion and cell proliferation were measured after IL-1 beta and PGE(2) incubation. Results: Myofibroblasts from both control and IPF fibroblast cultures stimulated with IL-1 beta showed no COX-2 expression. IPF fibroblasts showed increased myofibroblast population and reduced COX-2 expression in response to IL-1 beta. TGF-beta 1 increased the number of myofibroblasts in a time-dependent manner. In contrast, TGF-beta 1 induced slight COX-2 expression at 4 h (without increase in myofibroblasts) and 24 h, but not at 72 h. Both IPF and control cultures incubated with TGF-beta 1 for 72 h showed diminished COX-2 induction, PGE(2) secretion and alpha-SMA expression after IL-1 beta addition. The latter decreased proliferation in fibroblasts but not in myofibroblasts. A549 cells incubated with TGF-beta 1 for 72 h showed down-regulated COX-2 expression and low basal PGE(2) secretion in response to IL-1 beta. Immuno-histochemical analysis of IPF lung tissue showed no COX-2 immuno-reactivity in myofibroblast foci. Conclusions: Myofibroblasts are associated with COX-2 down-regulation and reduced PGE(2) production, which could be crucial in IPF development and progression.

Matèries

Fibrosi pulmonar, Immunofluorescència

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Pulmonary fibrosis, Immunofluorescence

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Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

Citació

GABASA FERRÀNDEZ, Marta, ROYO, Dolores, MOLINA MOLINA, María, ROCA I FERRER, Jordi, PUJOLS TARRÉS, Laura, PICADO VALLÉS, César, XAUBET MIR, Antonio, PEREDA, Javier. Lung Myofibroblasts Are Characterized by DownRegulated
Cyclooxygenase-2 and Its Main Metabolite,
Prostaglandin E2. _PLoS One_. 2013. Vol. 8, núm. 6, pàgs. e65445. [consulta: 29 de gener de 2026]. [Disponible a: https://hdl.handle.net/2445/126461]

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