Cadherin-11 Regulation of Fibrosis through Modulation of Epithelial-to-Mesenchymal Transition: Implications for Pulmonary Fibrosis in Scleroderma
Abstract
My laboratory focuses on the potential role of cadherin-11 (Cad11) in fibrosis. We have previously reported that Cad11expression is increased in fibrotic tissues from lungs of patients with idiopathic pulmonary fibrosis and skin of patients with systemic sclerosis. Subsequent studies have demonstrated that Cad11 is a critical mediator of lung and skin fibrosis using the intratracheal (IT) and subcutaneous bleomycin models. Preliminary studies suggest that Cad11 may regulate type 2 alveolar epithelial cell epithelial-to-mesenchymal transition (EMT), a process that contributes to the development of lung fibrosis. As opposed to the IT bleomycin lung fibrosis model, repeated administration of bleomycin via the intraperitoneal (IP) route is considered to better mimic human lung fibrosis and the process of EMT. This proposal builds on these recent observations and utilizes the IP bleomycin pulmonary fibrosis model. We hypothesize that Cad11 regulates the EMT in AEC during the development of pulmonary fibrosis and that cadherin-11 is therapeutic target in the intraperitoneal bleomycin model of pulmonary fibrosis. This proposal will be the first identify novel mechanisms by which Cad11 regulates EMT and build the foundation for additional translational studies seeking to develop Cad11 as a therapeutic target for SSc-ILD.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2016
- Accession Number
- AD1013617
Entities
People
- Sandeep K. Agarwal
Organizations
- Baylor College of Medicine