Systems biology approaches to understanding epithelial mesenchymal transition (EMT) in mucosal remodeling and signaling in asthma

Talha Ijaz, Konrad Pazdrak, Mridul Kalita, Rolf Konig, Sanjeev Choudhary, Bing Tian, Istvan Boldogh, Allan R. Brasier

Research output: Contribution to journalArticle

38 Citations (Scopus)

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.

Original languageEnglish (US)
Article number13
JournalWorld Allergy Organization Journal
Volume7
Issue number1
DOIs
StatePublished - Jun 2 2014

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Epithelial-Mesenchymal Transition
Systems Biology
Asthma
Extracellular Matrix
Myofibroblasts
Adaptive Immunity
Glucocorticoids
Cell Biology
Intercellular Signaling Peptides and Proteins
Oxidative Stress
Fibrosis
Epithelial Cells
Cytokines
Phenotype
Wounds and Injuries
Therapeutics

Keywords

  • EMT
  • Eosinophils
  • Inflammation
  • Innate immunity
  • NF-κB
  • Systems biology
  • TGFβ

ASJC Scopus subject areas

  • Immunology and Allergy

Cite this

Systems biology approaches to understanding epithelial mesenchymal transition (EMT) in mucosal remodeling and signaling in asthma. / Ijaz, Talha; Pazdrak, Konrad; Kalita, Mridul; Konig, Rolf; Choudhary, Sanjeev; Tian, Bing; Boldogh, Istvan; Brasier, Allan R.

In: World Allergy Organization Journal, Vol. 7, No. 1, 13, 02.06.2014.

Research output: Contribution to journalArticle

Ijaz, Talha ; Pazdrak, Konrad ; Kalita, Mridul ; Konig, Rolf ; Choudhary, Sanjeev ; Tian, Bing ; Boldogh, Istvan ; Brasier, Allan R. / Systems biology approaches to understanding epithelial mesenchymal transition (EMT) in mucosal remodeling and signaling in asthma. In: World Allergy Organization Journal. 2014 ; Vol. 7, No. 1.
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