Epithelial-to-mesenchymal Transition in Bronchial Epithelial Cells

Introduction: Epithelial-to-mesenchymal transition (EMT) is a crucial process during embryonic development as well as in wound repair and tissue regeneration. Thereby epithelial cells lose their polarity and become motile mesenchymal cells which are described to contribute to different diseases such as tissue fibrosis and cancer progression/metastasis. Disassembly of the junctional complexes and therewith the disruption of the epithelial barrier is an early event of EMT and necessary prior further changes leading to single cell invasion. Up to now, it remains elusive if the bronchial epithelium exhibits EMT potential in the course of lung disease and little is known about signaling pathways linking dissolution of tight junctions to this process.

Methods/Results: As in vitro cell culture model we used normal bronchial epithelial cells 16HBE. Upon TGFb treatment 16HBE cells were undergoing EMT-like process characterized by elevated levels of mesenchymal markers such as, fibronectin, SNAI1 and ZEB1. Cigarette smoke extract (CSE) had a major impact on 16HBE cell viability and was used to induce the cell injury. CSE disrupted cell-cell junctions and induced internalization of tight junction proteins occludin and ZO-1. We have developed an air-liquid interface cell culture model in order to resemble the in vivo conditions. When using the air-liquid interface model, the effect of TGFb and CSE together can now be assessed in more detail.

Outlook: In the future, the established in vitro model will be used to study signaling pathways activated during the tight junctions disassembly and their impact on EMT. To address the same questions in vivo, bleomycin and cigarette smoke mouse models will be used.