Lung Fibrosis

Currently approx. five million people are affected by pulmonary fibrosis worldwide. In most cases, patients are 40-50 years old at diagnosis, while the incidence of idiopathic pulmonary fibrosis increases drastically >50 years of age [84]. Fibrosis or fibrotic remodelling of lung tissue is a severe outcome of various lung diseases. Inflammatory cell invasion, epithelial cell injury and failure of re-epithelialization are followed by recruitment and persistence of fibroblasts. Excessive collagen and extracellular matrix production results in lung fibrosis [85]. Reduced PPAR expression was shown in lung fibroblasts of patients with dysregulated inflammation and fibrosis [86]. Studies found that TZDs were able to inhibit lung fibrosis [86]. PPAR ligands have negative effects on human lung fibroblasts by inhibiting proliferation and migration triggered by mitogenic growth factors such as PDGF [87]. Furthermore, PPAR agonists inhibit lung fibroblast differentiation mediated by

TGFp and significantly reduce the expression of fibronectin and type I collagen [88]. Anti-fibrotic effects of TZDs has been demonstrated in animal models even after strong pro-fibrotic exposure (i.e. bleomycin) confirming them as potential candidates for therapy [89].

 
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