Cadherin-11 regulates pulmonary fibrosis in bleomycin-induced lung injury (MUC5P.865)

Abstract

Abstract Idiopathic pulmonary fibrosis (IPF) is a progressive, irreversible pulmonary disorder with unknown effective treatment. IPF is characterized by excessive myofibroblast differentiation in the alveolar airways. Epithelial-to-mesenchymal transition (EMT) is the differentiation of fibroblast-like phenotype from epithelial cells resulting in myofibroblast accumulation. Cadherin-11 (Cad11) expression on hyperplastic alveolar epithelial cells is a novel finding in our lab. Hence, we hypothesized that Cad11 contributes to the development of pulmonary fibrosis through EMT. Our aims consist of determining: 1) The role of Cad-11 in EMT; and 2) The contribution of Cad11 deficiency and neutralization in the intraperitoneal (IP) bleomycin (BLM) model of pulmonary fibrosis. Preliminary findings show that deficiency and neutralization of Cad11 in this model is associated with attenuated pulmonary fibrosis and myofibroblast accumulation. In vitro studies demonstrated that Fc-Cad-11 was able to stimulate MLE-12 cell lines to produce Col1α expression while knockdown of Cad-11 via siRNA in these epithelial cell lines prevented the increase of fibrotic markers. These findings demonstrate that Cad-11 contributes to the development and progression of pulmonary fibrosis. The novelty of this project will be the identification of mechanisms by which Cad11 regulates EMT. This project will support additional translational studies to develop Cad11 as a therapeutic target for pulmonary fibrosis.