@article {ConfortiPA5401, author = {Franco Conforti and Robert Ridley and Mark Jones and Aiman Alzetani and Christopher Brereton and Yihua Wang and Paul Skipp and Luca Richeldi and Donna Davies}, title = {Late Breaking Abstract - Investigation of the epithelial-mesenchymal paracrine interactions in lung tissue repair and fibrosis}, volume = {54}, number = {suppl 63}, elocation-id = {PA5401}, year = {2019}, doi = {10.1183/13993003.congress-2019.PA5401}, publisher = {European Respiratory Society}, abstract = {Introduction: The lung epithelium is a functional interface between our body and the outside environment and it plays a key role in the respiratory physiology and pathology. Recurring alveolar epithelial injury is a hallmark of idiopathic pulmonary fibrosis (IPF) that lead to aberrant fibroblast activation resulting in the progressive destruction of the lung parenchymal architecture and impairment of gas exchange. The complex interactions between the persistent injured epithelium and the abnormal activated fibroblasts seems to be the main factors determining initiation and progression of the disease in association with aging, environmental exposure and genetic susceptibility. A better understanding of the epithelial-mesenchymal signaling in IPF is needed for the development of more efficient therapeutic strategies that promote restoration of normal epithelium integrity and limit the progression of fibrosis.Aim: Characterize the paracrine signaling between alveolar cells (AECs) and lung fibroblasts (FFs) and investigate its role in injury/repair of the epithelium.Methods: we established and characterize an ex-vivo co-culture models of AECs and FFs to mimic the epithelial-mesenchymal paracrine interaction in injured alveoli.Results and Conclusions: we detected abnormal epithelialization in co-culture of AECs and IPF FFs compared to co-culture of AECs and healthy FFs. Mass spectrometry analysis of fibroblasts secretome identified different extracellular matrix (ECM) proteins that are involved in tissue repair and fibrosis. Gene silencing of the ECM protein osteonectin in IPF FFs restored the alveolar epithelium homeostasis. These results suggest that IPF FFs secrete factors that alter the normal epithelial repair responses preventing the restoration of tissue homeostasis.FootnotesCite this article as: European Respiratory Journal 2019; 54: Suppl. 63, PA5401.This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).}, issn = {0903-1936}, URL = {https://erj.ersjournals.com/content/54/suppl_63/PA5401}, eprint = {https://erj.ersjournals.com/content}, journal = {European Respiratory Journal} }