Overlapping Effects of miR-21 Inhibition and Drugs for Idiopathic Pulmonary Fibrosis: Rationale for Repurposing Nintedanib as a Novel Treatment for Ischemia/Reperfusion Injury

ABSTRACT: A specific anti-miR-21 has emerged as an effective treatment for ischemia/reperfusion injury in a pig model of myocardial infarction (MI), but the perspectives for clinical translation are limited. Anti-miR-21 blunts profibrotic pathways, whose excessive activation is detrimental in the post-MI setting. Repurposing antifibrotic drugs approved for other indications is a possible strategy. We compared the molecular effects of anti-miR-21 and the 2 drugs approved for idiopathic pulmonary fibrosis (nintedanib and pirfenidone) through a bioinformatic approach. We report that nintedanib and anti-miR-21 share many targets, including the proto-oncogene Rous sarcoma oncogene cellular homolog. Conversely, pirfenidone and anti-miR-21 do not have common mechanisms of action. In summary, the molecular mechanisms activated by nintedanib are partially overlapping with those elicited by anti-miR-21. Nintedanib could be evaluated in animal studies or clinical trials on MI.