GSE4‐loaded nanoparticles a potential therapy for lung fibrosis that enhances pneumocyte growth, reduces apoptosis and DNA damage

Idiopathic pulmonary fibrosis is a lethal lung fibrotic disease, associated with aging with a mean survival of 2-5 years and no curative treatment. The GSE4 peptide is able to rescue cells from senescence, DNA and oxidative damage, inflammation, and induces telomerase activity. Here, we investigated...

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Autores: Pintado Berninches, Laura, Montes Worboys, Ana, Manguan García, Cristina, Arias Salgado, Elena G., Serrano, Adela, Fernandez Varas, Beatriz, Guerrero López, Rosa, Iarriccio, Laura, Planas Cerezales, Lurdes, Guenechea, Guillermo, Egusquiaguirre, Susana P., Hernandez, Rosa M., Igartua, Manoli, Luis Pedraz, Jose, Cortijo, Julio, Sastre, Leandro, Molina Molina, María, Perona, Rosario
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/176215
Acceso en línea:https://hdl.handle.net/2445/176215
Access Level:acceso abierto
Palabra clave:Fibrosi pulmonar
Nanopartícules
Pulmonary fibrosis
Nanoparticles
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spelling GSE4‐loaded nanoparticles a potential therapy for lung fibrosis that enhances pneumocyte growth, reduces apoptosis and DNA damagePintado Berninches, LauraMontes Worboys, AnaManguan García, CristinaArias Salgado, Elena G.Serrano, AdelaFernandez Varas, BeatrizGuerrero López, RosaIarriccio, LauraPlanas Cerezales, LurdesGuenechea, GuillermoEgusquiaguirre, Susana P.Hernandez, Rosa M.Igartua, ManoliLuis Pedraz, JoseCortijo, JulioSastre, LeandroMolina Molina, MaríaPerona, RosarioFibrosi pulmonarNanopartículesPulmonary fibrosisNanoparticlesIdiopathic pulmonary fibrosis is a lethal lung fibrotic disease, associated with aging with a mean survival of 2-5 years and no curative treatment. The GSE4 peptide is able to rescue cells from senescence, DNA and oxidative damage, inflammation, and induces telomerase activity. Here, we investigated the protective effect of GSE4 expression in vitro in rat alveolar epithelial cells (AECs), and in vivo in a bleomycin model of lung fibrosis. Bleomycin-injured rat AECs, expressing GSE4 or treated with GSE4-PLGA/PEI nanoparticles showed an increase of telomerase activity, decreased DNA damage, and decreased expression of IL6 and cleaved-caspase 3. In addition, these cells showed an inhibition in expression of fibrotic markers induced by TGF-β such as collagen-I and III among others. Furthermore, treatment with GSE4-PLGA/PEI nanoparticles in a rat model of bleomycin-induced fibrosis, increased telomerase activity and decreased DNA damage in proSP-C cells. Both in preventive and therapeutic protocols GSE4-PLGA/PEI nanoparticles prevented and attenuated lung damage monitored by SPECT-CT and inhibited collagen deposition. Lungs of rats treated with bleomycin and GSE4-PLGA/PEI nanoparticles showed reduced expression of α-SMA and pro-inflammatory cytokines, increased number of pro-SPC-multicellular structures and increased DNA synthesis in proSP-C cells, indicating therapeutic efficacy of GSE4-nanoparticles in experimental lung fibrosis and a possible curative treatment for lung fibrotic patients.Wiley2021202120212021info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion18 p.application/pdfhttps://hdl.handle.net/2445/176215Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.1096/fj.202001160RRThe FASEB Journal, 2021, vol. 35, num. 3https://doi.org/10.1096/fj.202001160RRcc by-nc-nd (c) Pintado Berninches et al., 2021http://creativecommons.org/licenses/by-nc-nd/3.0/es/info:eu-repo/semantics/openAccessoai:recercat.cat:2445/1762152026-05-29T05:05:01Z
dc.title.none.fl_str_mv GSE4‐loaded nanoparticles a potential therapy for lung fibrosis that enhances pneumocyte growth, reduces apoptosis and DNA damage
title GSE4‐loaded nanoparticles a potential therapy for lung fibrosis that enhances pneumocyte growth, reduces apoptosis and DNA damage
spellingShingle GSE4‐loaded nanoparticles a potential therapy for lung fibrosis that enhances pneumocyte growth, reduces apoptosis and DNA damage
Pintado Berninches, Laura
Fibrosi pulmonar
Nanopartícules
Pulmonary fibrosis
Nanoparticles
title_short GSE4‐loaded nanoparticles a potential therapy for lung fibrosis that enhances pneumocyte growth, reduces apoptosis and DNA damage
title_full GSE4‐loaded nanoparticles a potential therapy for lung fibrosis that enhances pneumocyte growth, reduces apoptosis and DNA damage
title_fullStr GSE4‐loaded nanoparticles a potential therapy for lung fibrosis that enhances pneumocyte growth, reduces apoptosis and DNA damage
title_full_unstemmed GSE4‐loaded nanoparticles a potential therapy for lung fibrosis that enhances pneumocyte growth, reduces apoptosis and DNA damage
title_sort GSE4‐loaded nanoparticles a potential therapy for lung fibrosis that enhances pneumocyte growth, reduces apoptosis and DNA damage
dc.creator.none.fl_str_mv Pintado Berninches, Laura
Montes Worboys, Ana
Manguan García, Cristina
Arias Salgado, Elena G.
Serrano, Adela
Fernandez Varas, Beatriz
Guerrero López, Rosa
Iarriccio, Laura
Planas Cerezales, Lurdes
Guenechea, Guillermo
Egusquiaguirre, Susana P.
Hernandez, Rosa M.
Igartua, Manoli
Luis Pedraz, Jose
Cortijo, Julio
Sastre, Leandro
Molina Molina, María
Perona, Rosario
author Pintado Berninches, Laura
author_facet Pintado Berninches, Laura
Montes Worboys, Ana
Manguan García, Cristina
Arias Salgado, Elena G.
Serrano, Adela
Fernandez Varas, Beatriz
Guerrero López, Rosa
Iarriccio, Laura
Planas Cerezales, Lurdes
Guenechea, Guillermo
Egusquiaguirre, Susana P.
Hernandez, Rosa M.
Igartua, Manoli
Luis Pedraz, Jose
Cortijo, Julio
Sastre, Leandro
Molina Molina, María
Perona, Rosario
author_role author
author2 Montes Worboys, Ana
Manguan García, Cristina
Arias Salgado, Elena G.
Serrano, Adela
Fernandez Varas, Beatriz
Guerrero López, Rosa
Iarriccio, Laura
Planas Cerezales, Lurdes
Guenechea, Guillermo
Egusquiaguirre, Susana P.
Hernandez, Rosa M.
Igartua, Manoli
Luis Pedraz, Jose
Cortijo, Julio
Sastre, Leandro
Molina Molina, María
Perona, Rosario
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Fibrosi pulmonar
Nanopartícules
Pulmonary fibrosis
Nanoparticles
topic Fibrosi pulmonar
Nanopartícules
Pulmonary fibrosis
Nanoparticles
description Idiopathic pulmonary fibrosis is a lethal lung fibrotic disease, associated with aging with a mean survival of 2-5 years and no curative treatment. The GSE4 peptide is able to rescue cells from senescence, DNA and oxidative damage, inflammation, and induces telomerase activity. Here, we investigated the protective effect of GSE4 expression in vitro in rat alveolar epithelial cells (AECs), and in vivo in a bleomycin model of lung fibrosis. Bleomycin-injured rat AECs, expressing GSE4 or treated with GSE4-PLGA/PEI nanoparticles showed an increase of telomerase activity, decreased DNA damage, and decreased expression of IL6 and cleaved-caspase 3. In addition, these cells showed an inhibition in expression of fibrotic markers induced by TGF-β such as collagen-I and III among others. Furthermore, treatment with GSE4-PLGA/PEI nanoparticles in a rat model of bleomycin-induced fibrosis, increased telomerase activity and decreased DNA damage in proSP-C cells. Both in preventive and therapeutic protocols GSE4-PLGA/PEI nanoparticles prevented and attenuated lung damage monitored by SPECT-CT and inhibited collagen deposition. Lungs of rats treated with bleomycin and GSE4-PLGA/PEI nanoparticles showed reduced expression of α-SMA and pro-inflammatory cytokines, increased number of pro-SPC-multicellular structures and increased DNA synthesis in proSP-C cells, indicating therapeutic efficacy of GSE4-nanoparticles in experimental lung fibrosis and a possible curative treatment for lung fibrotic patients.
publishDate 2021
dc.date.none.fl_str_mv 2021
2021
2021
2021
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/2445/176215
url https://hdl.handle.net/2445/176215
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/10.1096/fj.202001160RR
The FASEB Journal, 2021, vol. 35, num. 3
https://doi.org/10.1096/fj.202001160RR
dc.rights.none.fl_str_mv cc by-nc-nd (c) Pintado Berninches et al., 2021
http://creativecommons.org/licenses/by-nc-nd/3.0/es/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc by-nc-nd (c) Pintado Berninches et al., 2021
http://creativecommons.org/licenses/by-nc-nd/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 18 p.
application/pdf
dc.publisher.none.fl_str_mv Wiley
publisher.none.fl_str_mv Wiley
dc.source.none.fl_str_mv Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.812429

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