Anti-fibrotic effects of pirfenidone and rapamycin in primary IPF fibroblasts and human alveolar epithelial cells

Background: Pirfenidone, a pleiotropic anti-fibrotic treatment, has been shown to slow down disease progression of idiopathic pulmonary fibrosis (IPF), a fatal and devastating lung disease. Rapamycin, an inhibitor of fibroblast proliferation could be a potential anti-fibrotic drug to improve the eff...

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Autores: Molina-Molina, M, Machahua-Huamani, C, Vicens-Zygmunt, V, Llatjos, R, Escobar, I, Sala Llinàs, Ernest, Luburich-Hernaiz, P, Dorca, J, Montes-Worboys, A
Tipo de recurso: artículo
Fecha de publicación:2018
País:España
Institución:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/22534
Acceso en línea:https://hdl.handle.net/20.500.12105/22534
Access Level:acceso abierto
Palabra clave:Pirfenidone
Rapamycin
Idiopathic pulmonary fibrosis
Pulmonary fibrosis
Cell migration
Extracellular matrix proteins
Epithelial-mesenchymal transition
Factor de Crecimiento Transformador beta1
Movimiento Celular
Humanos
Biomarcadores
Miofibroblastos
Células Epiteliales Alveolares
Transición Epitelial-Mesenquimal
Sirolimus
Matriz Extracelular
Fibrosis Pulmonar Idiopática
Células A549
Piridonas
Alveolar Epithelial Cells
Biomarkers
Extracellular Matrix
Epithelial-Mesenchymal Transition
Idiopathic Pulmonary Fibrosis
Myofibroblasts
Pyridones
Cell Movement
Humans
Transforming Growth Factor beta1
A549 Cells
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spelling Anti-fibrotic effects of pirfenidone and rapamycin in primary IPF fibroblasts and human alveolar epithelial cellsMolina-Molina, MMachahua-Huamani, CVicens-Zygmunt, VLlatjos, REscobar, ISala Llinàs, ErnestLuburich-Hernaiz, PDorca, JMontes-Worboys, APirfenidoneRapamycinIdiopathic pulmonary fibrosisPulmonary fibrosisCell migrationExtracellular matrix proteinsEpithelial-mesenchymal transitionFactor de Crecimiento Transformador beta1Movimiento CelularHumanosBiomarcadoresMiofibroblastosCélulas Epiteliales AlveolaresTransición Epitelial-MesenquimalSirolimusMatriz ExtracelularFibrosis Pulmonar IdiopáticaCélulas A549PiridonasAlveolar Epithelial CellsBiomarkersExtracellular MatrixEpithelial-Mesenchymal TransitionIdiopathic Pulmonary FibrosisMyofibroblastsPyridonesCell MovementHumansTransforming Growth Factor beta1A549 CellsSirolimusBackground: Pirfenidone, a pleiotropic anti-fibrotic treatment, has been shown to slow down disease progression of idiopathic pulmonary fibrosis (IPF), a fatal and devastating lung disease. Rapamycin, an inhibitor of fibroblast proliferation could be a potential anti-fibrotic drug to improve the effects of pirfenidone. Methods: Primary lung fibroblasts from IPF patients and human alveolar epithelial cells (A549) were treated in vitro with pirfenidone and rapamycin in the presence or absence of transforming growth factor beta 1 (TGF-beta). Extracellular matrix protein and gene expression of markers involved in lung fibrosis (tenascin-c, fibronectin, collagen I (COM Al], collagen III [COL3A1] and alpha-smooth muscle actin [alpha-SMA]) were analyzed. A cell migration assay in pirfenidone, rapamycin and TGF-beta-containing media was performed. Results: Gene and protein expression of tenascin-c and fibronectin of fibrotic fibroblasts were reduced by pirfenidone or rapamycin treatment Pirfenidone-rapamycin treatment did not revert the epithelial to mesenchymal transition pathway activated by TGF-beta. However, the drug combination significantly abrogated fibroblast to myofibroblast transition. The inhibitory effect of pirfenidone on fibroblast migration in the scratch-wound assay was potentiated by rapamycin combination. Conclusions: These findings indicate that the combination of pirfenidone and rapamycin widen the inhibition range of fibrogenic markers and prevents fibroblast migration. These results would open a new line of research for an anti-fibrotic combination therapeutic approach.BioMed Central (BMC)20242024-09-0620182018-04-2720182018-04-27research articlehttp://purl.org/coar/resource_type/c_2df8fbb1info:eu-repo/semantics/articlehttps://hdl.handle.net/20.500.12105/22534reponame:Repisaludinstname:Instituto de Salud Carlos III (ISCIII)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:repisalud.isciii.es:20.500.12105/225342026-06-12T12:43:37Z
dc.title.none.fl_str_mv Anti-fibrotic effects of pirfenidone and rapamycin in primary IPF fibroblasts and human alveolar epithelial cells
title Anti-fibrotic effects of pirfenidone and rapamycin in primary IPF fibroblasts and human alveolar epithelial cells
spellingShingle Anti-fibrotic effects of pirfenidone and rapamycin in primary IPF fibroblasts and human alveolar epithelial cells
Molina-Molina, M
Pirfenidone
Rapamycin
Idiopathic pulmonary fibrosis
Pulmonary fibrosis
Cell migration
Extracellular matrix proteins
Epithelial-mesenchymal transition
Factor de Crecimiento Transformador beta1
Movimiento Celular
Humanos
Biomarcadores
Miofibroblastos
Células Epiteliales Alveolares
Transición Epitelial-Mesenquimal
Sirolimus
Matriz Extracelular
Fibrosis Pulmonar Idiopática
Células A549
Piridonas
Alveolar Epithelial Cells
Biomarkers
Extracellular Matrix
Epithelial-Mesenchymal Transition
Idiopathic Pulmonary Fibrosis
Myofibroblasts
Pyridones
Cell Movement
Humans
Transforming Growth Factor beta1
A549 Cells
Sirolimus
title_short Anti-fibrotic effects of pirfenidone and rapamycin in primary IPF fibroblasts and human alveolar epithelial cells
title_full Anti-fibrotic effects of pirfenidone and rapamycin in primary IPF fibroblasts and human alveolar epithelial cells
title_fullStr Anti-fibrotic effects of pirfenidone and rapamycin in primary IPF fibroblasts and human alveolar epithelial cells
title_full_unstemmed Anti-fibrotic effects of pirfenidone and rapamycin in primary IPF fibroblasts and human alveolar epithelial cells
title_sort Anti-fibrotic effects of pirfenidone and rapamycin in primary IPF fibroblasts and human alveolar epithelial cells
dc.creator.none.fl_str_mv Molina-Molina, M
Machahua-Huamani, C
Vicens-Zygmunt, V
Llatjos, R
Escobar, I
Sala Llinàs, Ernest
Luburich-Hernaiz, P
Dorca, J
Montes-Worboys, A
author Molina-Molina, M
author_facet Molina-Molina, M
Machahua-Huamani, C
Vicens-Zygmunt, V
Llatjos, R
Escobar, I
Sala Llinàs, Ernest
Luburich-Hernaiz, P
Dorca, J
Montes-Worboys, A
author_role author
author2 Machahua-Huamani, C
Vicens-Zygmunt, V
Llatjos, R
Escobar, I
Sala Llinàs, Ernest
Luburich-Hernaiz, P
Dorca, J
Montes-Worboys, A
author2_role author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv
dc.subject.none.fl_str_mv Pirfenidone
Rapamycin
Idiopathic pulmonary fibrosis
Pulmonary fibrosis
Cell migration
Extracellular matrix proteins
Epithelial-mesenchymal transition
Factor de Crecimiento Transformador beta1
Movimiento Celular
Humanos
Biomarcadores
Miofibroblastos
Células Epiteliales Alveolares
Transición Epitelial-Mesenquimal
Sirolimus
Matriz Extracelular
Fibrosis Pulmonar Idiopática
Células A549
Piridonas
Alveolar Epithelial Cells
Biomarkers
Extracellular Matrix
Epithelial-Mesenchymal Transition
Idiopathic Pulmonary Fibrosis
Myofibroblasts
Pyridones
Cell Movement
Humans
Transforming Growth Factor beta1
A549 Cells
Sirolimus
topic Pirfenidone
Rapamycin
Idiopathic pulmonary fibrosis
Pulmonary fibrosis
Cell migration
Extracellular matrix proteins
Epithelial-mesenchymal transition
Factor de Crecimiento Transformador beta1
Movimiento Celular
Humanos
Biomarcadores
Miofibroblastos
Células Epiteliales Alveolares
Transición Epitelial-Mesenquimal
Sirolimus
Matriz Extracelular
Fibrosis Pulmonar Idiopática
Células A549
Piridonas
Alveolar Epithelial Cells
Biomarkers
Extracellular Matrix
Epithelial-Mesenchymal Transition
Idiopathic Pulmonary Fibrosis
Myofibroblasts
Pyridones
Cell Movement
Humans
Transforming Growth Factor beta1
A549 Cells
Sirolimus
description Background: Pirfenidone, a pleiotropic anti-fibrotic treatment, has been shown to slow down disease progression of idiopathic pulmonary fibrosis (IPF), a fatal and devastating lung disease. Rapamycin, an inhibitor of fibroblast proliferation could be a potential anti-fibrotic drug to improve the effects of pirfenidone. Methods: Primary lung fibroblasts from IPF patients and human alveolar epithelial cells (A549) were treated in vitro with pirfenidone and rapamycin in the presence or absence of transforming growth factor beta 1 (TGF-beta). Extracellular matrix protein and gene expression of markers involved in lung fibrosis (tenascin-c, fibronectin, collagen I (COM Al], collagen III [COL3A1] and alpha-smooth muscle actin [alpha-SMA]) were analyzed. A cell migration assay in pirfenidone, rapamycin and TGF-beta-containing media was performed. Results: Gene and protein expression of tenascin-c and fibronectin of fibrotic fibroblasts were reduced by pirfenidone or rapamycin treatment Pirfenidone-rapamycin treatment did not revert the epithelial to mesenchymal transition pathway activated by TGF-beta. However, the drug combination significantly abrogated fibroblast to myofibroblast transition. The inhibitory effect of pirfenidone on fibroblast migration in the scratch-wound assay was potentiated by rapamycin combination. Conclusions: These findings indicate that the combination of pirfenidone and rapamycin widen the inhibition range of fibrogenic markers and prevents fibroblast migration. These results would open a new line of research for an anti-fibrotic combination therapeutic approach.
publishDate 2018
dc.date.none.fl_str_mv 2018
2018-04-27
2018
2018-04-27
2024
2024-09-06
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/20.500.12105/22534
url https://hdl.handle.net/20.500.12105/22534
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv BioMed Central (BMC)
publisher.none.fl_str_mv BioMed Central (BMC)
dc.source.none.fl_str_mv reponame:Repisalud
instname:Instituto de Salud Carlos III (ISCIII)
instname_str Instituto de Salud Carlos III (ISCIII)
reponame_str Repisalud
collection Repisalud
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,812429

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