Collagen remodelling in pulmonary diseases

Abstract

Fibrillar collagens act as biological scaffolds in every organ in the body. The amount of collagens are known to be altered in pulmonary diseases such as chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) but the structural changes of these collagens are not well understood. The experiments in this thesis revealed an altered collagen maturity/organisation in COPD and IPF that may be regulated by lysyl oxidase (LO) enzymes (LOX, LOXL1-4). Collagen maturity/organisation was decreased in the large airways of severe COPD. LOX was found to be a potential regulator of collagen maturity/organisation in the airways. LOXL1 expression was suppressed in non-COPD-smokers but was not changed in COPD-smokers; excessive collagen remodelling mediated by LOXL1 may lead to fibrosis around COPD airways. In IPF parenchyma collagen maturity/organisation was increased and correlated positively with the increased LOXL1-2 but negatively with the decreased LOX. The relative expression of the LOs and inter-relationship with collagen maturity/organisation was found to be significant in IPF. This thesis also elucidated a potential mechanism for LO inhibition in the treatment of fibrosis. The findings in this thesis enhance our understanding of collagen structural remodelling in COPD and IPF and the role of LOs in the disease pathology