PRRX (Paired Related Homeobox Protein)-1 as a novel and key transcription factor in lung fibrosis: in search for innovative targets. – FibroPRX

Adult respiratory diseases are a major burden in terms of morbidity and mortality and, particularly as related to chronic respiratory disease, are of increasing concern. This project is focused on a lethal chronic lung disease that displays mesenchymal compartment dysregulation: idiopathic pulmonary fibrosis (IPF). Indeed, idiopathic pulmonary fibrosis is the most common form of pulmonary fibrosis. IPF is defined as a specific form of chronic, progressive fibrosing interstitial pneumonia of unknown cause. IPF patients have an overall median survival of 3 to 5 years. It has been proposed that IPF results from an aberrant activation of alveolar epithelial cells that provokes excessive migration, proliferation and activation of mesenchymal cells with the formation of myofibroblastic foci and excessive deposition of extracellular matrix (ECM). With the exception of lung transplantation, no therapy has been proven beneficial with respect to survival for IPF. Indeed, the only two drugs recently approved in IPF (namely pirfenidone and nintedanib) appear to only slow disease progression. Our preliminary results identified the transcription factors (TFs) Paired Related Homeobox proteins 1 (PRRX1) that are required for proper mesenchymal cell fate during development, as potential key regulators in IPF. Hence, we plan to demonstrate from patients to mice that the PRRX1 TFs are potential therapeutic targets in IPF using in vitro, ex vivo organotypic culture and in vivo models. We are confident that our project will help to better understand the physiopathology of lung fibrosis.