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

Abstract

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.

• Authors: Duitman JanWillem, Cong Lin, Sophie Moog, Madeleine Jaillet, Yves Castier, Aurélie Cazes, Keren S Borensztajn, Bruno Crestani, C Arnold Spek
• Journal: Journal of clinical and translational research (J Clin Transl Res) Vol. 3 Issue Suppl 2 Pg. 358-365 (Jul 30 2018) ISSN: 2424-810X [Electronic] Singapore
• PMID: 30873483 (Publication Type: Journal Article)