Idiopathic pulmonary fibrosis (IPF) is a devastating disease with median survival of 2.5-3.5 years after diagnosis. The causes and molecular pathogenesis of persistent extracellular matrix production and collagen deposition in idiopathic pulmonary fibrosis still remain unclear. Novel treatments for this restrictive lung disease are limited, and available ones, e.g. nintedanib and pirfenidone, only delay the progression of IPF. Molecular targets for the treatment of IPF have delineated the anti-fibrotic properties of a family of nuclear hormone receptors known as peroxisome proliferator-activated receptors (PPARs), amongst which the PPAR-γ isotype was mainly investigated. Only limited information is available on the roles of PPAR-α in IPF and no studies are yet available on PPAR δ/β in pulmonary fibrosis. Additionally, oxidative stress, caused by an increase of reactive oxygen species (ROS), is an important triggering factor influencing the molecular pathogenesis of IPF. The prospects of antioxidants as combined therapy with other treatment regimens for IPF and the regulatory roles of PPARs on peroxisomal genes call for the exploration of catalase function, the major antioxidative enzyme in peroxisomes, in IPF fibroblasts. Also the influence of metabolites of peroxisomal β-oxidation in the molecular pathogenesis of IPF is completely unknown. In view of this, the potential roles of PPAR-mediated peroxisomal anti-oxidative function and β-oxidation products in IPF were explored in this thesis. Using primary human lung fibroblasts from control and IPF patients as well as lung biopsies from patients and bleomycin-treated mice, the beneficial anti-fibrotic properties of PPAR-delta/β (and its combination with PPAR-γ), peroxisomal β-oxidation products and catalase were demonstrated. In summary, PPAR-β in combination with PPAR-γ reversed the fibrotic phenotype, increased peroxisomal biogenesis and peroxisomal β-oxidation. Peroxisome-derived docosahexaenoic acid is involved in the regulation of intracellular collagen I levels and peroxisomal catalase plays important role in the regulation of intra- and extracellular collagen. The study therefore underscores potential therapeutic roles of peroxisomes in the prevention of IPF progression.
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