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Pharmacol Ther. 2014 Mar;141(3):250-60. doi: 10.1016/j.pharmthera.2013.10.008. Epub 2013 Oct 25.

Novel therapeutic strategies for lung disorders associated with airway remodelling and fibrosis.

Author information

1
Fibrosis Laboratory, Department of Pharmacology, Monash University, Clayton, Victoria 3800, Australia; Departments of Pathology and Pharmacology and Therapeutics, University of Melbourne, Parkville, Victoria 3010, Australia. Electronic address: simon.royce@monash.edu.
2
Department of Respiratory and Sleep Medicine, School of Medicine and Pharmacology, Royal Perth Hospital, University of Western Australia, Perth 6000, Western Australia, Australia.
3
Fibrosis Laboratory, Department of Pharmacology, Monash University, Clayton, Victoria 3800, Australia; Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Victoria 3010, Australia; Department of Biochemistry and Molecular Biology, University of Melbourne, Parkville, Victoria 3010, Australia. Electronic address: chrishan.samuel@monash.edu.

Abstract

Inflammatory cell infiltration, cytokine release, epithelial damage, airway/lung remodelling and fibrosis are central features of inflammatory lung disorders, which include asthma, chronic obstructive pulmonary disease, acute respiratory distress syndrome and idiopathic pulmonary fibrosis. Although the lung has some ability to repair itself from acute injury, in the presence of ongoing pathological stimuli and/or insults that lead to chronic disease, it no longer retains the capacity to heal, resulting in fibrosis, the final common pathway that causes an irreversible loss of lung function. Despite inflammation, genetic predisposition/factors, epithelial-mesenchymal transition and mechanotransduction being able to independently contribute to airway remodelling and fibrosis, current therapies for inflammatory lung diseases are limited by their ability to only target the inflammatory component of the disease without having any marked effects on remodelling (epithelial damage and fibrosis) that can cause lung dysfunction independently of inflammation. Furthermore, as subsets of patients suffering from these diseases are resistant to currently available therapies (such as corticosteroids), novel therapeutic approaches are required to combat all aspects of disease pathology. This review discusses emerging therapeutic approaches, such as trefoil factors, relaxin, histone deacetylase inhibitors and stem cells, amongst others that have been able to target airway inflammation and airway remodelling while improving related lung dysfunction. A better understanding of the mode of action of these therapies and their possible combined effects may lead to the identification of their clinical potential in the setting of lung disease, either as adjunct or alternative therapies to currently available treatments.

KEYWORDS:

Epithelial damage; Fibrosis; HDAC inhibitors; Inflammatory lung diseases; Relaxin; Stem cells; TFF2

[Indexed for MEDLINE]

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