Pathological airway remodelling in inflammation

Authors


  • Ethics
    All studies we have referred to have been reviewed by ethics committee and have been approved.

  • Conflicts of interest
    This article forms part of a supplement sponsored by GlaxoSmithKline. OH has received two research grants from AstraZeneca 2006 and 2008. GMV, KL, LB, KN, AAS and GWT have no competing interests.

  • Authorship
    GWT has participated in the design, carried out the review and written and revised the article draft. KL, KN, AAS, OH, GMV and LB have participated in the design, commented on drafts versions of the article, and approved the final version.

Prof. Gunilla Westergren-Thorsson, Department of Experimental Medical Science, Division of Vascular and Airway Research, Lund University, BMC D12, S-22184
Lund, Sweden.
Tel: +46 46 222 33 14
Fax: +46 46 222 31 28
email: gunilla.westergren-thorsson@med.lu.se

Abstract

Introduction:  Airway remodelling refers to a wide pattern of patophysiological mechanisms involving smooth muscle cell hyperplasia, increase of activated fibroblasts and myofibroblasts with deposition of extracellular matrix. In asthma, it includes alterations of the epithelial cell layer with goblet cell hyperplasia, thickening of basement membranes, peri-bronchial and peri-broncheolar fibrosis. Moreover, airway remodelling occurs not only in asthma but also in several pulmonary disorders such as chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis and systemic sclerosis. Asthma treatment with inhaled corticosteroids does not fully prevent airway remodelling and thus have restricted influence on the natural course of the disease.

Objectives:  This review highlights the role of different fibroblast phenotypes and potential origins of these cells in airway remodelling.

Results:  During inflammatory conditions, such as asthma, fibroblasts can differentiate into an active, more contractile phenotype termed myofibroblast, with expression of stress fibres and alpha-smooth muscle actin. The origin of myofibroblasts has lately been debated, and three sources have been identified: recruitment and differentiation of resident tissue fibroblasts; fibrocytes – circulating progenitor cells; and epithelial–mesenchymal transition.

Conclusion:  It is clear that airway mesenchymal cells, including fibroblasts/myofibroblasts, are more dynamic in terms of differentiation and origin than has previously been recognised. Considering that these cells are key players in the remodelling process, it is of utmost importance to characterise specific markers for the various fibroblast phenotypes and to explore factors that drive the differentiation to develop future diagnostic and therapeutic tools for asthma patients.

Please cite this paper as: Westergren-Thorsson G, Larsen K, Nihlberg K, Andersson-Sjöland A, Hallgren O, Marko-Varga G and Bjermer L. Pathological airway remodelling in inflammation. Clin Respir J 2010; 4 (Suppl. 1): 1–8.

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