JanWillem Duitman, Cong Lin, Sophie Moog, Madeleine Jaillet, Yves Castier, Aurélie Cazes, Keren S. Borensztajn, Bruno Crestani, C. Arnold Spek

Duitman et al., J Clin Transl Res, 2017, 3(S2): 4

Published online: February 21, 2018


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.

DOI: http://dx.doi.org/10.18053/jctres.03.2017S2.004  

Author affiliation

1 Inserm UMR1152, Medical School Xavier Bichat, Paris, France
2 Université Paris Diderot, Sorbonne Paris Cité, Département Hospitalo-universitaire FIRE (Fibrosis, Inflammation and Remodeling) and LabEx Inflamex, Paris, France
3 Assistance Publique-Hôpitaux de Paris (APHP), Hôpital Bichat, Service de Pneumologie A, Paris, France
4 INSERM UMR _S933, Université Pierre et Marie Curie, Paris, France
5 Center for Experimental and Molecular Medicine, Academic Medical Center, Amsterdam, the Netherlands

*Corresponding author
JanWillem Duitman
Inserm UMR1152, Medical School Xavier Bichat, Paris, France
Email: jan-willem.duitman@inserm.fr

Handling editor:

Michal Heger
Department of Experimental Surgery, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands


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