CCAAT/enhancer binding protein delta (C/EBPδ) deficiency does not affect bleomycin-induced pulmonary fibrosis
Journal Title: Journal of Clinical and Translational Research - Year 2018, Vol 3, Issue 2
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 and Affiliations
JanWillem Duitman, Cong Lin, Sophie Moog, Madeleine Jaillet, Yves Castier, Aurélie Cazes, Keren S. Borensztajn, Bruno Crestani, C. Arnold Spek
Keywords
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