Characterising epithelial to mesenchymal transition and pro-fibrotic processes in chronic obstructive pulmonary disease
type: CreativeWork
description: Background RationaleChronic Obstructive Pulmonary Disease (COPD) is an irreversible disease reducing lung function via processes of inflammation, emphysema and fibrosis. Patient treatment options are limited including bronchodilators and inhaled corticosteroids that are poorly effective. Linked with a significant history of cigarette smoking, pathology is characterised by recruitment of inflammatory cells to the lung (alveolar macrophages, neutrophils and lymphocytes: TH1 and CD8); dysregulated neutrophils and macrophages release tissue lysing proteases causing enlargement of airspaces (emphysema). Most severe pathology includes dysregulated epithelial repair and overgrowth of lung fibroblasts (fibrosis). The source of fibroblasts is not clear. Fibrosis in renal, liver and heart disease is partly mediated by epithelial-mesenchymal transition (EMT) differentiation whereby epithelia acquire fibrotic biomarkers such as desmin, S100A4 and α-smooth muscle actin. In lung fibrosis this has not been characterised, further the molecular mechanisms in the lung are poorly understood. Identifying these processes is key to developing improved future therapeutic interventions. AimsTo characterise human COPD lungs for expression of EMT biomarkers compared to control subjects to determine the processes of lung fibrosis in COPD. Further, to identify the signalling mechanisms within the EMT tissue to identify the regulatory processes that may be intervened in future therapies. Finally, to assess primary human fibroblast responses to cigarette smoke extract (CSE) and stretch forces to establish a new model of emphysema and lung fibrosis for future research.MethodsPatients were recruited from the North West Lung Centre at the University Hospital of South Manchester who were undergoing lobectomy surgery as part of their normal clinical care. Lung resections were prepared for histochemical analysis by formalin fixing and wax embedding. 5ul microtome slices were immunohistochemically stai…
abstract: Background RationaleChronic Obstructive Pulmonary Disease (COPD) is an irreversible disease reducing lung function via processes of inflammation, emphysema and fibrosis. Patient treatment options are limited including bronchodilators and inhaled corticosteroids that are poorly effective. Linked with a significant history of cigarette smoking, pathology is characterised by recruitment of inflammatory cells to the lung (alveolar macrophages, neutrophils and lymphocytes: TH1 and CD8); dysregulated neutrophils and macrophages release tissue lysing proteases causing enlargement of airspaces (emphysema). Most severe pathology includes dysregulated epithelial repair and overgrowth of lung fibroblasts (fibrosis). The source of fibroblasts is not clear. Fibrosis in renal, liver and heart disease is partly mediated by epithelial-mesenchymal transition (EMT) differentiation whereby epithelia acquire fibrotic biomarkers such as desmin, S100A4 and α-smooth muscle actin. In lung fibrosis this has not been characterised, further the molecular mechanisms in the lung are poorly understood. Identifying these processes is key to developing improved future therapeutic interventions. AimsTo characterise human COPD lungs for expression of EMT biomarkers compared to control subjects to determine the processes of lung fibrosis in COPD. Further, to identify the signalling mechanisms within the EMT tissue to identify the regulatory processes that may be intervened in future therapies. Finally, to assess primary human fibroblast responses to cigarette smoke extract (CSE) and stretch forces to establish a new model of emphysema and lung fibrosis for future research.MethodsPatients were recruited from the North West Lung Centre at the University Hospital of South Manchester who were undergoing lobectomy surgery as part of their normal clinical care. Lung resections were prepared for histochemical analysis by formalin fixing and wax embedding. 5ul microtome slices were immunohistochemically stai…
author: Carlin, Helen Victoria
language: en
date published: 2026
date modified: 2026-07-24T04:26:44Z
provider: U. of Salford
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: U. of Salford