Antifibrotic property of pemafibrate during bleomycin-induced lung fibrosis

<bold>Background:</bold> Drugs for metabolic diseases such as statins and metformin have been demonstrated to mitigate the lung fibrosis development in experimental settings. The PPAR family is known to have a variety of physiological functions including regulation of lipid metabolism, intracellular signal transduction, and inflammatory response. Pemafibrate, a selective PPARα modulator for hyperlipidemia, may also possess an antifibrotic property, but its precise mechanism remains to be elucidated. <bold>Aims and objectives:</bold> To elucidate the antifibrotic mechanisms of pemafibrate for attenuating pulmonary fibrosis development. <bold>Methods:</bold> The antifibrotic effect of pemafibrate was examined by detecting myofibroblast differentiation during TGF-β treatment in lung fibroblasts. The antifibrotic effect of pemafibrate was also evaluated by using bleomycin (BLM)-induced lung fibrosis mouse models. <bold>Results:</bold> Pemafibrate suppressed TGF-β-mediated myofibroblast differentiation and cellular senescence progression in lung fibroblasts. Administration of pemafibrate mixed diet reduced lung fibrosis development (hydroxyproline assay and Ashcroft score) in BLM models. In addition, inhalation therapy of nebulized pemafibrate also mitigated BLM-induced lung fibrosis, suggesting the potential efficacy of pemafibrate via lung local administration. <bold>Conclusions:</bold> Pemafibrate may be a promising candidate drug for preventing lung fibrosis. We are currently working to elucidate the antifibrotic mechanism of pemafibrate in association with PPARα activation.