Abstract

Background. miRNAs are important regulators in a variety of pulmonary disorders and multiple evidence demonstrates their dysregulation in the lungs of IPF patients and animal models of lung fibrosis. Aims and objectives. With the aim to identify differentially expressed miRNAs and clarify their potential role in the development and progression of pulmonary fibrosis, we investigated the time-dependent changes in specific miRNAs expression in rat and mouse bleomycin (BLM) models. Moreover, the therapeutic effect of Nintedanib was evaluated in both models. Methods. Male SD rats and C57BL/6 mice received a double BLM administration or its vehicle (saline) and were sacrificed every week up to day 28 (rats) and 21 (mice). According to therapeutic regimen, Nintedanib was orally administered from day 7 post-BLM in a group of animals, at the respective doses of 100 (rats) and 60 mg/kg/day (mice). Total RNA was isolated from lungs and fibrosis-focused miScript miRNA PCR Arrays (Qiagen) were used to investigate a panel of 84 specific miRNAs. Results. Bleomycin induced a mostly down-regulated miRNAs profile in both species, which was more persistent between 21- and 28-days post BLM in rats and between 7 and 14 days in mice. Moreover, we identified a subset of deregulated miRNAs (=1.5 fold) in common between the two different models demonstrating similarities in animal models. Particularly, for two up-regulated (e.g miRNA21) and three down-regulated miRNAs (e.g miRNA29), Nintedanib treatment attenuated their dysregulation. Conclusions. These data may contribute to a better understanding of the molecular mechanisms underlying lung fibrosis.