Abstract
Idiopathic pulmonary fibrosis (IPF) is a fatal condition that reduces life expectancy and shows a limited response to available therapies. Pirfenidone has been approved for treatment of IPF, but little is known about the distinct metabolic changes that occur in the lung upon pirfenidone administration. Here, we performed a proof-of-concept study using high-resolution quantitative Matrix-Assisted Laser Desorption/Ionization Fourier-Transform Ion Cyclotron Resonance-Mass Spectrometry Imaging (MALDI-FTICR-MSI) to simultaneously detect, visualise, and quantify in situ endogenous and exogenous metabolites in lungs of mice subjected to experimental fibrosis and human patients with IPF and to assess the effect of pirfenidone treatment on metabolite levels. Metabolic pathway analysis and endogenous metabolite quantification revealed that pirfenidone treatment restores redox imbalance and glycolysis in IPF tissues, and down-regulates ascorbate and aldarate metabolism, thereby likely contributing to in situ modulation of collagen processing. As such, we detected specific alterations in metabolite pathways in fibrosis, and importantly, metabolic recalibration following pirfenidone treatment. Together, these results highlight the suitability of high-resolution MALDI-FTICR-MSI for deciphering the therapeutic effects of pirfenidone and provide a preliminary analysis of the metabolic changes that occur during pirfenidone treatment in vivo. These data may therefore contribute to improvement of currently available therapies for IPF.
Footnotes
This manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.
Conflict of interest: Dr. Sun has nothing to disclose.
Conflict of interest: Dr. Fernandez has nothing to disclose.
Conflict of interest: Dr. Wei has nothing to disclose.
Conflict of interest: Dr. Witting has nothing to disclose.
Conflict of interest: Dr. Aichler has nothing to disclose.
Conflict of interest: Dr. Feuchtinger has nothing to disclose.
Conflict of interest: Dr. Burgstaller has nothing to disclose.
Conflict of interest: Dr. Verleden has nothing to disclose.
Conflict of interest: Prof. Dr. Schmitt-Kopplin has nothing to disclose.
Conflict of interest: Dr. Eickelberg has nothing to disclose.
Conflict of interest: Dr. Walch has nothing to disclose.
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