Increased AGE-RAGE ratio in idiopathic pulmonary fibrosis

Background: the abnormal epithelial-mesenchymal restorative capacity in idiopathic pulmonary fibrosis (IPF) has been recently associated with an accelerated aging process as a key point for the altered wound healing. The advanced glycation end-products (AGEs) are the consequence of non-enzymatic rea...

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Autores: Machahua, Carlos, Montes Worboys, Ana, Llatjós, Roger, Escobar Campuzano, Ignacio, Dorca i Sargatal, Jordi, Molina Molina, María, Vicens Zygmunt, Vanesa
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2016
País:España
Recursos:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/132949
Acesso em linha:https://hdl.handle.net/2445/132949
Access Level:acceso abierto
Palavra-chave:Matriu extracel·lular
Envelliment
Fibrosi pulmonar
Immunohistoquímica
Extracellular matrix
Aging
Pulmonary fibrosis
Immunohistochemistry
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spelling Increased AGE-RAGE ratio in idiopathic pulmonary fibrosisMachahua, CarlosMontes Worboys, AnaLlatjós, RogerEscobar Campuzano, IgnacioDorca i Sargatal, JordiMolina Molina, MaríaVicens Zygmunt, VanesaMatriu extracel·lularEnvellimentFibrosi pulmonarImmunohistoquímicaExtracellular matrixAgingPulmonary fibrosisImmunohistochemistryBackground: the abnormal epithelial-mesenchymal restorative capacity in idiopathic pulmonary fibrosis (IPF) has been recently associated with an accelerated aging process as a key point for the altered wound healing. The advanced glycation end-products (AGEs) are the consequence of non-enzymatic reactions between lipid and protein with several oxidants in the aging process. The receptor for AGEs (RAGEs) has been implicated in the lung fibrotic process and the alveolar homeostasis. However, this AGE-RAGE aging pathway has been under-explored in IPF. Methods: lung samples from 16 IPF and 9 control patients were obtained through surgical lung biopsy. Differences in AGEs and RAGE expression between both groups were evaluated by RT-PCR, Western blot and immunohistochemistry. The effect of AGEs on cell viability of primary lung fibrotic fibroblasts and alveolar epithelial cells was assessed. Cell transformation of fibrotic fibroblasts cultured into glycated matrices was evaluated in different experimental conditions. Results: our study demonstrates an increase of AGEs together with a decrease of RAGEs in IPF lungs, compared with control samples. Two specific AGEs involved in aging, pentosidine and Nε-Carboxymethyl lysine, were significantly increased in IPF samples. The immunohistochemistry identified higher staining of AGEs related to extracellular matrix (ECM) proteins and the apical surface of the alveolar epithelial cells (AECs) surrounding fibroblast foci in fibrotic lungs. On the other hand, RAGE location was present at the cell membrane of AECs in control lungs, while it was almost missing in pulmonary fibrotic tissue. In addition, in vitro cultures showed that the effect of AGEs on cell viability was different for AECs and fibrotic fibroblasts. AGEs decreased cell viability in AECs, even at low concentration, while fibroblast viability was less affected. Furthermore, fibroblast to myofibroblast transformation could be enhanced by ECM glycation. Conclusions: all of these findings suggest a possible role of the increased ratio AGEs-RAGEs in IPF, which could be a relevant accelerating aging tissue reaction in the abnormal wound healing of the lung fibrotic process.BioMed Central2016info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/132949Articles publicats en revistes (Ciències Clíniques)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.1186/s12931-016-0460-2Respiratory Research, 2016, vol. 17, p. 144https://doi.org/10.1186/s12931-016-0460-2cc-by (c) Machahua-Huamani, Carlos et al., 2016http://creativecommons.org/licenses/by/3.0/esinfo:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1329492026-05-27T06:46:51Z
dc.title.none.fl_str_mv Increased AGE-RAGE ratio in idiopathic pulmonary fibrosis
title Increased AGE-RAGE ratio in idiopathic pulmonary fibrosis
spellingShingle Increased AGE-RAGE ratio in idiopathic pulmonary fibrosis
Machahua, Carlos
Matriu extracel·lular
Envelliment
Fibrosi pulmonar
Immunohistoquímica
Extracellular matrix
Aging
Pulmonary fibrosis
Immunohistochemistry
title_short Increased AGE-RAGE ratio in idiopathic pulmonary fibrosis
title_full Increased AGE-RAGE ratio in idiopathic pulmonary fibrosis
title_fullStr Increased AGE-RAGE ratio in idiopathic pulmonary fibrosis
title_full_unstemmed Increased AGE-RAGE ratio in idiopathic pulmonary fibrosis
title_sort Increased AGE-RAGE ratio in idiopathic pulmonary fibrosis
dc.creator.none.fl_str_mv Machahua, Carlos
Montes Worboys, Ana
Llatjós, Roger
Escobar Campuzano, Ignacio
Dorca i Sargatal, Jordi
Molina Molina, María
Vicens Zygmunt, Vanesa
author Machahua, Carlos
author_facet Machahua, Carlos
Montes Worboys, Ana
Llatjós, Roger
Escobar Campuzano, Ignacio
Dorca i Sargatal, Jordi
Molina Molina, María
Vicens Zygmunt, Vanesa
author_role author
author2 Montes Worboys, Ana
Llatjós, Roger
Escobar Campuzano, Ignacio
Dorca i Sargatal, Jordi
Molina Molina, María
Vicens Zygmunt, Vanesa
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Matriu extracel·lular
Envelliment
Fibrosi pulmonar
Immunohistoquímica
Extracellular matrix
Aging
Pulmonary fibrosis
Immunohistochemistry
topic Matriu extracel·lular
Envelliment
Fibrosi pulmonar
Immunohistoquímica
Extracellular matrix
Aging
Pulmonary fibrosis
Immunohistochemistry
description Background: the abnormal epithelial-mesenchymal restorative capacity in idiopathic pulmonary fibrosis (IPF) has been recently associated with an accelerated aging process as a key point for the altered wound healing. The advanced glycation end-products (AGEs) are the consequence of non-enzymatic reactions between lipid and protein with several oxidants in the aging process. The receptor for AGEs (RAGEs) has been implicated in the lung fibrotic process and the alveolar homeostasis. However, this AGE-RAGE aging pathway has been under-explored in IPF. Methods: lung samples from 16 IPF and 9 control patients were obtained through surgical lung biopsy. Differences in AGEs and RAGE expression between both groups were evaluated by RT-PCR, Western blot and immunohistochemistry. The effect of AGEs on cell viability of primary lung fibrotic fibroblasts and alveolar epithelial cells was assessed. Cell transformation of fibrotic fibroblasts cultured into glycated matrices was evaluated in different experimental conditions. Results: our study demonstrates an increase of AGEs together with a decrease of RAGEs in IPF lungs, compared with control samples. Two specific AGEs involved in aging, pentosidine and Nε-Carboxymethyl lysine, were significantly increased in IPF samples. The immunohistochemistry identified higher staining of AGEs related to extracellular matrix (ECM) proteins and the apical surface of the alveolar epithelial cells (AECs) surrounding fibroblast foci in fibrotic lungs. On the other hand, RAGE location was present at the cell membrane of AECs in control lungs, while it was almost missing in pulmonary fibrotic tissue. In addition, in vitro cultures showed that the effect of AGEs on cell viability was different for AECs and fibrotic fibroblasts. AGEs decreased cell viability in AECs, even at low concentration, while fibroblast viability was less affected. Furthermore, fibroblast to myofibroblast transformation could be enhanced by ECM glycation. Conclusions: all of these findings suggest a possible role of the increased ratio AGEs-RAGEs in IPF, which could be a relevant accelerating aging tissue reaction in the abnormal wound healing of the lung fibrotic process.
publishDate 2016
dc.date.none.fl_str_mv 2016
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/2445/132949
url https://hdl.handle.net/2445/132949
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/s12931-016-0460-2
Respiratory Research, 2016, vol. 17, p. 144
https://doi.org/10.1186/s12931-016-0460-2
dc.rights.none.fl_str_mv cc-by (c) Machahua-Huamani, Carlos et al., 2016
http://creativecommons.org/licenses/by/3.0/es
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Machahua-Huamani, Carlos et al., 2016
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
publisher.none.fl_str_mv BioMed Central
dc.source.none.fl_str_mv Articles publicats en revistes (Ciències Clíniques)
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
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score 15,301603

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