The Role of Bone Morphogenetic Protein Signalling in Adult Lung Health and Disease
type: CreativeWork
description: Bone morphogenetic protein (BMP) signalling is essential for correct lung morphogenesis. The pathway controls branching morphogenesis in the nascent lung and is also involved in the establishment of correct epithelial cell distribution throughout the airways. In the adult lung, BMP signalling is reactivated during airway injury and inflammation and there is evidence of aberrant signalling in lung cancer and in chronic lung diseases such as asthma and fibrosis. However, little is known about the role of BMP signalling in healthy adult airways. Furthermore the effect of incorrect BMP pathway expression during epithelial repair and inflammatory and malignant lung diseases remains elusive. The aims of this project were to characterise BMP pathway expression in the descending airways of large animal models and to investigate the role of BMP signalling during adult airway homeostasis, recovery and disease. To investigate the role of BMP signalling in malignant lung disease we used a heterogeneous lung cancer cell line DLKP. We explored the effect of the BMP pathway on epithelial-to-mesenchymal (EMT) progression and phenotypic plasticity between the tumour subpopulations. BMP-4 treatment induced mesenchymal-like projections in the DLKP-SQ clones and significant morphological changes in the DLKP-M clones towards the stem-cell like colonies of DLKP-I populations. Elevated N-cadherin and Vimentin protein expression was also evident in the clones following BMP-4 treatment. By stably transfecting an E-cadherin gene in these E-cadherin-null cells we demonstrated the distinct phenotypic differences between these tumour subpopulations. Healthy porcine and rhesus macaque lungs were used to characterise BMP pathway expression throughout the airways. Active BMP signalling was present in the descending airway epithelium and a gradient in pathway activation along the proximal-distal axis of the lungs was observed [1]. Using a primary porcine tracheal in vitro explant model the BMP sign…
abstract: Bone morphogenetic protein (BMP) signalling is essential for correct lung morphogenesis. The pathway controls branching morphogenesis in the nascent lung and is also involved in the establishment of correct epithelial cell distribution throughout the airways. In the adult lung, BMP signalling is reactivated during airway injury and inflammation and there is evidence of aberrant signalling in lung cancer and in chronic lung diseases such as asthma and fibrosis. However, little is known about the role of BMP signalling in healthy adult airways. Furthermore the effect of incorrect BMP pathway expression during epithelial repair and inflammatory and malignant lung diseases remains elusive. The aims of this project were to characterise BMP pathway expression in the descending airways of large animal models and to investigate the role of BMP signalling during adult airway homeostasis, recovery and disease. To investigate the role of BMP signalling in malignant lung disease we used a heterogeneous lung cancer cell line DLKP. We explored the effect of the BMP pathway on epithelial-to-mesenchymal (EMT) progression and phenotypic plasticity between the tumour subpopulations. BMP-4 treatment induced mesenchymal-like projections in the DLKP-SQ clones and significant morphological changes in the DLKP-M clones towards the stem-cell like colonies of DLKP-I populations. Elevated N-cadherin and Vimentin protein expression was also evident in the clones following BMP-4 treatment. By stably transfecting an E-cadherin gene in these E-cadherin-null cells we demonstrated the distinct phenotypic differences between these tumour subpopulations. Healthy porcine and rhesus macaque lungs were used to characterise BMP pathway expression throughout the airways. Active BMP signalling was present in the descending airway epithelium and a gradient in pathway activation along the proximal-distal axis of the lungs was observed [1]. Using a primary porcine tracheal in vitro explant model the BMP sign…
author: Lynn, Thérése Marion
language: en
date published: 2015
date modified: 2026-07-24T03:02:54Z
provider: National University of Ireland - Maynooth
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: National University of Ireland Maynooth