Investigation of the epithelial-mesenchymal trophic unit in idiopathic pulmonary fibrosis

Introduction: Idiopathic pulmonary fibrosis (IPF) is a progressive disease with a poor prognosis and limited therapeutic options. Increasing evidence suggests that alveolar epithelial damage and resulting abnormal epithelial-mesenchymal crosstalk may contribute to the aberrant wound healing response observed in the lungs of IPF patients. The epithelial-mesenchymal trophic unit (EMTU) describes the functional interactions between epithelial cells, mesenchymal cells and the ECM which are necessary to regulate lung development, repair of damaged tissue and inflammatory responses. Thus characterization of EMTU in IPF will help to understand the pathofisiology of the disease. Aim: Characterize the paracrine crosstalk between alveolar cells (AECs) and lung fibroblasts (FFs) and investigate its role in injury and repair of the epithelium. Methods: we enstablished an ex-vivo co-culture models of AECs and FFs to mimic the EMTU of the respiratory epithelium. Epithelial cell layer intergrity was assed by immunofluorescence. Oxidative stress and injury/repair response were analysed using qPCR, western blot and time-laspe microscopy. Results and Conclusions: we detected abnormal epithelialization in co-culture of AECs and IPF FFs compared to co-culture of AECs and healthy FFs while western blot and qPCR data show increase in markers of cell motility. These results suggest that IPF FFs alter the normal epithelial repair responses preventing the restoration of lung tissue homeostasis. Therefore characterization of the EMTU in IPF will help the development of more efficient therapeutic strategies to limit the progression of fibrosis and promote restoration of the normal lung epithelium in IPF patients.