Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/132949
Title: Increased AGE-RAGE ratio in idiopathic pulmonary fibrosis
Author: Machahua-Huamani, Carlos
Montes-Worboys, Ana
Llatjós, Roger
Escobar Campuzano, Ignacio
Dorca i Sargatal, Jordi
Molina-Molina, María
Vicens-Zygmunt, Vanesa
Keywords: Matriu extracel·lular
Envelliment
Fibrosi pulmonar
Immunohistoquímica
Extracellular matrix
Aging
Pulmonary fibrosis
Immunohistochemistry
Issue Date: 5-Nov-2016
Publisher: BioMed Central
Abstract: 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.
Note: Reproducció del document publicat a: https://doi.org/10.1186/s12931-016-0460-2
It is part of: Respiratory Research, 2016, vol. 17, p. 144
URI: http://hdl.handle.net/2445/132949
Related resource: https://doi.org/10.1186/s12931-016-0460-2
ISSN: 1465-993X
Appears in Collections:Articles publicats en revistes (Ciències Clíniques)
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

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