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, María, Machahua, Carlos, Vicens Zygmunt, Vanesa, Llatjós, Roger, Escobar, I., Sala Llinàs, Ernest, Luburich Hernaiz, Patricio, Dorca i Sargatal, Jordi, Montes Worboys, Ana
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2018
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/123933
Acceso en línea:https://hdl.handle.net/2445/123933
Access Level:acceso abierto
Palabra clave:Fibrosi pulmonar
Matriu extracel·lular
Terapèutica
Therapeutics
Pulmonary fibrosis
Extracellular matrix
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spelling Anti-fibrotic Effects Of Pirfenidone And Rapamycin In Primary Ipf Fibroblasts And Human Alveolar Epithelial CellsMolina Molina, MaríaMachahua, CarlosVicens Zygmunt, VanesaLlatjós, RogerEscobar, I.Sala Llinàs, ErnestLuburich Hernaiz, PatricioDorca i Sargatal, JordiMontes Worboys, AnaFibrosi pulmonarMatriu extracel·lularTerapèuticaTherapeuticsPulmonary fibrosisExtracellular matrixBackground: 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 Ltd2018info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/123933Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.1186/s12890-018-0626-4Bmc Pulmonary Medicine, 2018, Vol. 18:63https://doi.org/10.1186/s12890-018-0626-4cc-by (c) Molina-Molina, María et al., 2018http://creativecommons.org/licenses/by/3.0/es/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1239332026-05-27T06:46:51Z
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, María
Fibrosi pulmonar
Matriu extracel·lular
Terapèutica
Therapeutics
Pulmonary fibrosis
Extracellular matrix
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, María
Machahua, Carlos
Vicens Zygmunt, Vanesa
Llatjós, Roger
Escobar, I.
Sala Llinàs, Ernest
Luburich Hernaiz, Patricio
Dorca i Sargatal, Jordi
Montes Worboys, Ana
author Molina Molina, María
author_facet Molina Molina, María
Machahua, Carlos
Vicens Zygmunt, Vanesa
Llatjós, Roger
Escobar, I.
Sala Llinàs, Ernest
Luburich Hernaiz, Patricio
Dorca i Sargatal, Jordi
Montes Worboys, Ana
author_role author
author2 Machahua, Carlos
Vicens Zygmunt, Vanesa
Llatjós, Roger
Escobar, I.
Sala Llinàs, Ernest
Luburich Hernaiz, Patricio
Dorca i Sargatal, Jordi
Montes Worboys, Ana
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Fibrosi pulmonar
Matriu extracel·lular
Terapèutica
Therapeutics
Pulmonary fibrosis
Extracellular matrix
topic Fibrosi pulmonar
Matriu extracel·lular
Terapèutica
Therapeutics
Pulmonary fibrosis
Extracellular matrix
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
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/123933
url https://hdl.handle.net/2445/123933
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1186/s12890-018-0626-4
Bmc Pulmonary Medicine, 2018, Vol. 18:63
https://doi.org/10.1186/s12890-018-0626-4
dc.rights.none.fl_str_mv cc-by (c) Molina-Molina, María et al., 2018
http://creativecommons.org/licenses/by/3.0/es/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Molina-Molina, María et al., 2018
http://creativecommons.org/licenses/by/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Biomed Central Ltd
publisher.none.fl_str_mv Biomed Central Ltd
dc.source.none.fl_str_mv Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869424657076060160
score 15,301603

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