Lomas, Nicola Jane (2013) Semi-quantitative immunohistochemical exploration of lung tissue remodelling in idiopathic pulmonary fibrosis. Masters thesis, Keele University.

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Abstract

Aim: This thesis explores the complex cellular and biological interrelationships involved in Idiopathic Pulmonary Fibrosis (IPF) lung tissue remodelling using immunohistochemical analysis. Methods and results: 21 IPF and 19 control lung tissues were examined for expression and localisation of key pathogenic markers implicated in Epithelial Mesenchymal Transition (EMT), proliferation, and cell cycle within alveolar type II cells (ATII cells) and fibroblastic foci. E-cadherin was expressed in IPF and control ATII cells (mean expression score >75%). In IPF, mean expression of N-cadherin was scanty (mean expression score <10%): however 4 cases demonstrated augmented expression in ATII cells correlating to histological disease status (as reflected by number of fibroblastic foci) (Pearson correlation score 0.557). Transforming growth factor-β (TGF-β) protein expression was significantly increased in IPF ATII cells with variable expression within fibroblastic foci. The proliferation marker Ki-67 was observed within hyperplastic ATII cells but not in cells overlying foci. IPF ATII cells demonstrated variable Surfactant protein-C (SP-C). Hyperplastic ATII cells overlying fibroblastic foci expressed Cyclin D1, p53, p21WAF1, SOCS3 and p16INK4A. Conclusions: There is inconclusive evidence to support the role of EMT in the pathogenesis of IPF. Histological analysis suggests TGF-β-stimulated myofibroblasts initiate a contractile response within established fibroblastic foci leading to mechanical stress on the surrounding alveolar epithelium. My data provides evidence of potential TGF-β-mediated contact inhibition of ATII cells overlying fibroblastic foci, leading to prolonged cell stasis and subsequent senescence. This ATII cell senescence may lead to a reduction in the lung tissue remodelling capacity of IPF epithelium within the micro-niche areas surrounding fibroblastic foci. Information derived from this study may be used to develop targeted interventions aimed at reducing the number of fibroblastic foci and therefore improving ATII cell regeneration of the alveolar epithelium. Marker expression correlation with histological disease activity may emerge as future prognostic indicators for IPF.

Item Type: Thesis (Masters)
Subjects: R Medicine > RC Internal medicine
Divisions: Faculty of Medicine and Health Sciences > Institute for Science and Technology in Medicine
Contributors: Spiteri, Monica (Thesis advisor)
Depositing User: Lisa Bailey
Date Deposited: 16 Aug 2022 14:29
Last Modified: 16 Aug 2022 14:29
URI: https://eprints.keele.ac.uk/id/eprint/11299

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