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CCAAT/enhancer binding protein delta (C/EBPδ) deficiency does not affect bleomycin-induced pulmonary fibrosis

BACKGROUND: Idiopathic pulmonary fibrosis is a devastating fibrotic diffuse parenchymal lung disorder that remains refractory to pharmacological therapies. Therefore, novel treatments are urgently required. CCAAT/enhancer binding protein delta (C/EBPδ) is a transcription factor that mediates critica...

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Autores principales: JanWillem, Duitman, Lin, Cong, Moog, Sophie, Jaillet, Madeleine, Castier, Yves, Cazes, Aurélie, Borensztajn, Keren S., Crestani, Bruno, Spek, C. Arnold
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Whioce Publishing Pte. Ltd. 2018
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6412614/
https://www.ncbi.nlm.nih.gov/pubmed/30873483
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author JanWillem, Duitman
Lin, Cong
Moog, Sophie
Jaillet, Madeleine
Castier, Yves
Cazes, Aurélie
Borensztajn, Keren S.
Crestani, Bruno
Spek, C. Arnold
author_facet JanWillem, Duitman
Lin, Cong
Moog, Sophie
Jaillet, Madeleine
Castier, Yves
Cazes, Aurélie
Borensztajn, Keren S.
Crestani, Bruno
Spek, C. Arnold
author_sort JanWillem, Duitman
collection PubMed
description BACKGROUND: Idiopathic pulmonary fibrosis is a devastating fibrotic diffuse parenchymal lung disorder that remains refractory to pharmacological therapies. Therefore, novel treatments are urgently required. CCAAT/enhancer binding protein delta (C/EBPδ) is a transcription factor that mediates critical cellular functions in pathophysiology and which was recently suggested to be a key regulatory component in IPF. The purpose of this study was to prove or refute the importance of C/EBPδ in pulmonary fibrosis. METHODS: Pulmonary fibrosis was induced by intranasal instillation of bleomycin into wild-type and C/EBPδ deficient mice. At different time intervals after bleomycin instillation, fibrosis was assessed by hydroxyproline analysis, histochemistry and q-PCR for fibrotic marker expression. RESULTS: C/EBPδ deficient mice developed pulmonary fibrosis to a similar degree as wildtype mice as evident from similar Ashcroft scores, hydroxyproline levels and expression levels of collagen, fibronectin and α-smooth muscle actin at both 14 and 21 days after bleomycin instillation. The resolution of fibrosis, assessed at 48 days after bleomycin instillation, was also similar in wildtype and C/EBPδ deficient mice. In line with the lack of effect of C/EBPδ on fibrosis progression/resolution, macrophage recruitment and/or differentiation were also not different in wildtype or C/EBPδ deficient mice. CONCLUSIONS: Overall, C/EBPδ does not seem to affect bleomycin-induced experimental pulmonary fibrosis and we challenge the importance of C/EBPδ in pulmonary fibrosis. RELEVANCE FOR PATIENTS: This study shows that the transcription factor C/EBPδ does not play a major role in the development of pulmonary fibrosis. Pharmacological targeting of C/EBPδ is therefore not likely to have a beneficial effect for patients suffering from pulmonary fibrosis.
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spelling pubmed-64126142019-03-14 CCAAT/enhancer binding protein delta (C/EBPδ) deficiency does not affect bleomycin-induced pulmonary fibrosis JanWillem, Duitman Lin, Cong Moog, Sophie Jaillet, Madeleine Castier, Yves Cazes, Aurélie Borensztajn, Keren S. Crestani, Bruno Spek, C. Arnold J Clin Transl Res Special Issue Article BACKGROUND: Idiopathic pulmonary fibrosis is a devastating fibrotic diffuse parenchymal lung disorder that remains refractory to pharmacological therapies. Therefore, novel treatments are urgently required. CCAAT/enhancer binding protein delta (C/EBPδ) is a transcription factor that mediates critical cellular functions in pathophysiology and which was recently suggested to be a key regulatory component in IPF. The purpose of this study was to prove or refute the importance of C/EBPδ in pulmonary fibrosis. METHODS: Pulmonary fibrosis was induced by intranasal instillation of bleomycin into wild-type and C/EBPδ deficient mice. At different time intervals after bleomycin instillation, fibrosis was assessed by hydroxyproline analysis, histochemistry and q-PCR for fibrotic marker expression. RESULTS: C/EBPδ deficient mice developed pulmonary fibrosis to a similar degree as wildtype mice as evident from similar Ashcroft scores, hydroxyproline levels and expression levels of collagen, fibronectin and α-smooth muscle actin at both 14 and 21 days after bleomycin instillation. The resolution of fibrosis, assessed at 48 days after bleomycin instillation, was also similar in wildtype and C/EBPδ deficient mice. In line with the lack of effect of C/EBPδ on fibrosis progression/resolution, macrophage recruitment and/or differentiation were also not different in wildtype or C/EBPδ deficient mice. CONCLUSIONS: Overall, C/EBPδ does not seem to affect bleomycin-induced experimental pulmonary fibrosis and we challenge the importance of C/EBPδ in pulmonary fibrosis. RELEVANCE FOR PATIENTS: This study shows that the transcription factor C/EBPδ does not play a major role in the development of pulmonary fibrosis. Pharmacological targeting of C/EBPδ is therefore not likely to have a beneficial effect for patients suffering from pulmonary fibrosis. Whioce Publishing Pte. Ltd. 2018-02-21 /pmc/articles/PMC6412614/ /pubmed/30873483 Text en Copyright © 2015, Whioce Publishing Pte. Ltd. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. This work is licensed under a Creative Commons Attribution 4.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Special Issue Article
JanWillem, Duitman
Lin, Cong
Moog, Sophie
Jaillet, Madeleine
Castier, Yves
Cazes, Aurélie
Borensztajn, Keren S.
Crestani, Bruno
Spek, C. Arnold
CCAAT/enhancer binding protein delta (C/EBPδ) deficiency does not affect bleomycin-induced pulmonary fibrosis
title CCAAT/enhancer binding protein delta (C/EBPδ) deficiency does not affect bleomycin-induced pulmonary fibrosis
title_full CCAAT/enhancer binding protein delta (C/EBPδ) deficiency does not affect bleomycin-induced pulmonary fibrosis
title_fullStr CCAAT/enhancer binding protein delta (C/EBPδ) deficiency does not affect bleomycin-induced pulmonary fibrosis
title_full_unstemmed CCAAT/enhancer binding protein delta (C/EBPδ) deficiency does not affect bleomycin-induced pulmonary fibrosis
title_short CCAAT/enhancer binding protein delta (C/EBPδ) deficiency does not affect bleomycin-induced pulmonary fibrosis
title_sort ccaat/enhancer binding protein delta (c/ebpδ) deficiency does not affect bleomycin-induced pulmonary fibrosis
topic Special Issue Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6412614/
https://www.ncbi.nlm.nih.gov/pubmed/30873483
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