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Eur Respir J. 2018 Nov 22;52(5). pii: 1800564. doi: 10.1183/13993003.00564-2018. Print 2018 Nov.

Transcriptome profiling reveals the complexity of pirfenidone effects in idiopathic pulmonary fibrosis.

Author information

Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Austria.
Otto Loewi Research Center, Medical University of Graz, Graz, Austria.
Joint lead authors.
Dept of Internal Medicine, Universities of Giessen and Marburg Lung Center, Giessen, Germany.
Members of the German Center for Lung Research.
Dept of Thoracic Surgery, Medical University of Vienna, Vienna, Austria.
Dept of Biochemistry, Universities of Giessen and Marburg Lung Center, Giessen, Germany.
Dept of Surgery, Universities of Giessen and Marburg Lung Center, Giessen, Germany.
Goethe University School of Medicine, Frankfurt am Main, Germany.
Translational Research Unit, Thoraxklinik University Hospital Heidelberg, Heidelberg, Germany.
Center for Interstitial and Rare Lung Diseases Pneumology and Respiratory Critical Care Medicine, Thoraxklinik University of Heidelberg, Translational Lung Research Center Heidelberg (TLRC), Heidelberg, Germany.
Dept of Pulmonology, Medical University of Graz, Graz, Austria.


Despite the beneficial effects of pirfenidone in treating idiopathic pulmonary fibrosis (IPF), it remains unclear if lung fibroblasts (FB) are the main therapeutic target.To resolve this question, we employed a comparative transcriptomic approach and analysed lung homogenates (LH) and FB derived from IPF patients treated with or without pirfenidone.In FB, pirfenidone therapy predominantly affected growth and cell division pathways, indicating a major cellular metabolic shift. In LH samples, pirfenidone treatment was mostly associated with inflammation-related processes. In FB and LH, regulated genes were over-represented in the Gene Ontology node "extracellular matrix". We identified lower expression of cell migration-inducing and hyaluronan-binding protein (CEMIP) in both LH and FB from pirfenidone-treated IPF patients. Plasma levels of CEMIP were elevated in IPF patients compared to healthy controls and decreased after 7 months of pirfenidone treatment. CEMIP expression in FB was downregulated in a glioma-associated oncogene homologue-dependent manner and CEMIP silencing in IPF FB reduced collagen production and attenuated cell proliferation and migration.Cumulatively, our approach indicates that pirfenidone exerts beneficial effects via its action on multiple pathways in both FB and other pulmonary cells, through its ability to control extracellular matrix architecture and inflammatory reactions.

Conflict of interest statement

Conflict of interest: A. Olschewski reports grants and honoraria for speaking from Pfizer, outside the submitted work. Conflict of interest: W. Seeger reports personal fees from Pfizer, Novartis, United Therapeutics, Actelion, Vectura, Savara, Medspray and Bayer AG, outside the submitted work. Conflict of interest: H. Olschewski reports grants from Intermune/Roche, and grants and personal fees from Boehringer, outside the submitted work. All other authors have nothing to disclose.

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