title: Systems biology approaches to understanding Epithelial Mesenchymal Transition (EMT) in mucosal remodeling and signaling in asthma.
abstract: A pathological hallmark of asthma is chronic injury and repair, producing dysfunction of the epithelial barrier function. In this setting, increased oxidative stress, growth factor- and cytokine stimulation, together with extracellular matrix contact produces transcriptional reprogramming of the epithelial cell. This process results in epithelial-mesenchymal transition (EMT), a cellular state associated with loss of epithelial polarity, expression of mesenchymal markers, enhanced mobility and extracellular matrix remodeling. As a result, the cellular biology of the EMT state produces characteristic changes seen in severe, refractory asthma: myofibroblast expansion, epithelial trans-differentiation and subepithelial fibrosis. EMT also induces profound changes in epithelial responsiveness that affects innate immune signaling that may have impact on the adaptive immune response and effectiveness of glucocorticoid therapy in severe asthma. We discuss how this complex phenotype is beginning to be understood using systems biology-level approaches through perturbations coupled with high throughput profiling and computational modeling. Understanding the distinct changes induced by EMT at the systems level may provide translational strategies to reverse the altered signaling and physiology of refractory asthma.
authors: Department of Biochemistry and Molecular Biology, The University of Texas Medical Branch, 301 University Blvd, Galveston 77555-1060, Texas, USA.
authors: Talha
authors: T
authors: Ijaz
authors: Department of Biochemistry and Molecular Biology, The University of Texas Medical Branch, 301 University Blvd, Galveston 77555-1060, Texas, USA.|Sealy Center for Molecular Medicine, The University of Texas Medical Branch, 301 University Blvd, Galveston 77555-1060, Texas, USA.|Institute for Translational Sciences, The University of Texas Medical Branch, 301 University Blvd, Galveston 77555-1060, Texas, USA.
authors: Konrad
authors: K
authors: Pazdrak
authors: Sealy Center for Molecular Medicine, The University of Texas Medical Branch, 301 University Blvd, Galveston 77555-1060, Texas, USA.|Department of Internal Medicine, The University of Texas Medical Branch, 301 University Blvd, Galveston 77555-1060, Texas, USA.
authors: Mridul
authors: M
authors: Kalita
authors: Sealy Center for Molecular Medicine, The University of Texas Medical Branch, 301 University Blvd, Galveston 77555-1060, Texas, USA.|Department of Microbiology and Immunology, The University of Texas Medical Branch, 301 University Blvd, Galveston 77555-1060, Texas, USA.
authors: Rolf
authors: R
authors: Konig
authors: Department of Biochemistry and Molecular Biology, The University of Texas Medical Branch, 301 University Blvd, Galveston 77555-1060, Texas, USA.|Sealy Center for Molecular Medicine, The University of Texas Medical Branch, 301 University Blvd, Galveston 77555-1060, Texas, USA.|Department of Microbiology and Immunology, The University of Texas Medical Branch, 301 University Blvd, Galveston 77555-1060, Texas, USA.
authors: Sanjeev
authors: S
authors: Choudhary
authors: Department of Internal Medicine, The University of Texas Medical Branch, 301 University Blvd, Galveston 77555-1060, Texas, USA.
authors: Bing
authors: B
authors: Tian
authors: Department of Biochemistry and Molecular Biology, The University of Texas Medical Branch, 301 University Blvd, Galveston 77555-1060, Texas, USA.|Sealy Center for Molecular Medicine, The University of Texas Medical Branch, 301 University Blvd, Galveston 77555-1060, Texas, USA.|Department of Microbiology and Immunology, The University of Texas Medical Branch, 301 University Blvd, Galveston 77555-1060, Texas, USA.
authors: Istvan
authors: I
authors: Boldogh
authors: Sealy Center for Molecular Medicine, The University of Texas Medical Branch, 301 University Blvd, Galveston 77555-1060, Texas, USA.|Institute for Translational Sciences, The University of Texas Medical Branch, 301 University Blvd, Galveston 77555-1060, Texas, USA.|Department of Internal Medicine, The University of Texas Medical Branch, 301 University Blvd, Galveston 77555-1060, Texas, USA.
authors: Allan R
authors: AR
authors: Brasier
keywords: EMT; Eosinophils; Inflammation; Innate immunity; NF-κB; Systems biology; TGFβ