Epithelial-Mesenchymal-Transition : a proposed mechanism in the development of Bronchiolitis Obliterans
For patients with end-stage lung disease, lung transplantation is their only hope for survival. Unfortunately, some of the lung transplant recipients (LTRs) might face obstacles following lung transplantation, one of which is chronic lung transplant rejection also known as bronchiolitis obliterans (BO) histologically and bronchiolitis obliterans syndrome (BOS) clinically. The exact etiology behind BO development remains poorly understood. Speculations have suggested the involvement of epithelial cells in the airway remodeling process leading to airway obstruction. One of the proposed mechanisms is a transitional process, known as epithelial-mesenchymal-transition (EMT). In this process epithelial cells lose their properties and acquire mesenchymal ones causing them to be more mobile and invasive which allow them to take part of the airway remodeling process in BO. Induction of EMT can be due to several factors such as inflammation, apoptosis. In our study we try to detect in vivo the presence of EMT in transbronchial biopsies (TBB) obtained from LTRs and associates it with their clinical conditions. We also try to manipulate and induce EMT in vitro in small airway epithelial cells (SAEC) using conditioned apoptotic (SSC4h) and non apoptotic (ZVAD) media produced from human microvascular endothelial cells (HMVEC) from lung. In addition, we worked on detecting possible mediators such as connective-tissue growth factor (CTGF), transforming growth factor-beta (TGF-β), and perlecan in produced media.
Lung transplantation Chronic rejection Epithelial-mesenchymal-transition Transbronchial biopsies Apoptosis