Endotracheal FGF19 limits bleomycin-induced pulmonary fibrosis in mice : an innovative treatment of pulmonary fibrosis?

The systemic overexpression of FGF19 was demonstrated to have antifibrotic properties in a mouse model of bleomycin-induced fibrosis (1). We aimed to determine the effect of a lung targeted FGF19 treatment on bleomycin-induced pulmonary fibrosis. Methods: C57BL/6 wild type mice received a unique endotracheal injection of bleomycin (40µg) at D0, then were injected endotracheally with lipid nanoparticule (LNP)-formulated FGF19 mRNA 0.2mg/ml (collaboration with Translate Bio) at D7 and D10 and sacrificed at D14. Control mice received a non-specific (NS) mRNA LNP. FGF19 concentration was determined in bronchoalveolar lavage fluid (BAL) and plasma by ELISA. Results: FGF19 was detected in BAL in all mice receiving LNP FGF19 mRNA, but was never detected in plasma. Survival was similar in both groups, while weight loss was reduced in the FGF19 mRNA-treated group as compared to the NS mRNA group. Lung injury scores, and lung mRNA content of Fn1, Col1a1, Col3a1, Acta2, Elastin and Tenascin C, were lower in the FGF19 mRNA group as compared to the NS mRNA group. However, this effect was not confirmed at protein level. Lung mRNA content for Pai-1 and Ctgf were decreased after LNP FGF19 mRNA. Conclusion: Our data indicate a potential protective effect of an endotracheal FGF19 mRNA treatment on bleomycin-induced pulmonary fibrosis. If our results are confirmed, inhaled FGF19 could represent an innovative therapy in IPF. Reference : (1) Justet et al. Am J Respir Cell Mol Biol 2022; 67(2):173-187.