Therapeutic targets in lung tissue remodelling and fibrosis.

Gang Liu, Ashleigh M Philp, Tamera Corte, Mark A Travis, Heidi Schilter, Nicole G Hansbro, Chris J Burns, Mathew S Eapen, Sukhwinder S Sohal, Janette K Burgess, Philip M Hansbro

Journal: Pharmacology & therapeutics 2021;225():107839

PMID: 33774068

Full Text on Elsevier Science View on PubMed

Abstract

Structural changes involving tissue remodelling and fibrosis are major features of many pulmonary diseases, including asthma, chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF). Abnormal deposition of extracellular matrix (ECM) proteins is a key factor in the development of tissue remodelling that results in symptoms and impaired lung function in these diseases. Tissue remodelling in the lungs is complex and differs between compartments. Some pathways are common but tissue remodelling around the airways and in the parenchyma have different morphologies. Hence it is critical to evaluate both common fibrotic pathways and those that are specific to different compartments; thereby expanding the understanding of the pathogenesis of fibrosis and remodelling in the airways and parenchyma in asthma, COPD and IPF with a view to developing therapeutic strategies for each. Here we review the current understanding of remodelling features and underlying mechanisms in these major respiratory diseases. The differences and similarities of remodelling are used to highlight potential common therapeutic targets and strategies. One central pathway in remodelling processes involves transforming growth factor (TGF)-β induced fibroblast activation and myofibroblast differentiation that increases ECM production. The current treatments and clinical trials targeting remodelling are described, as well as potential future directions. These endeavours are indicative of the renewed effort and optimism for drug discovery targeting tissue remodelling and fibrosis.

Address: Centre for Inflammation, Centenary Institute and University of Technology Sydney, Sydney, NSW, Australia.; Centre for Inflammation, Centenary Institute and University of Technology Sydney, Sydney, NSW, Australia; St Vincent's Medical School, UNSW Medicine, UNSW, Sydney, NSW, Australia.; Royal Prince Alfred Hospital, Camperdown, NSW, Australia; Sydney Medical School, University of Sydney, Sydney, NSW, Australia.; The Lydia Becker Institute of Immunology and Inflammation, Faculty of Biology, Medicine and Health, Manchester Academic Health Sciences Centre and Wellcome Trust Centre for Cell-Matrix Research, University of Manchester, Manchester, United Kingdom.; Pharmaxis Ltd, 20 Rodborough Road, Frenchs Forest, Sydney, NSW, Australia.; Walter and Eliza Hall Institute of Medical Research, Department of Medical Biology, The University of Melbourne, Melbourne, VIC 3010, Australia.; Respiratory Translational Research Group, Department of Laboratory Medicine, School of Health Sciences, University of Tasmania, Launceston, TAS, Australia.; University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD (GRIAC), Department of Pathology and Medical Biology, Groningen, The Netherlands; Woolcock Institute of Medical Research, Discipline of Pharmacology, The University of Sydney, Sydney, NSW, Australia.; Centre for Inflammation, Centenary Institute and University of Technology Sydney, Sydney, NSW, Australia. Electronic address: [email protected].

DOI: 10.1016/j.pharmthera.2021.107839

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MeSH Terms: Airway Remodeling, Asthma, Calcium-Binding Proteins, Extracellular Matrix, Fibroblasts, Fibrosis, Glycoproteins, Humans, Idiopathic Pulmonary Fibrosis, Lung Diseases, Matrix Metalloproteinases, Pulmonary Disease, Chronic Obstructive, Transforming Growth Factor beta