Pathological airway remodelling in inflammation.
BACKGROUND
Airway remodelling refers to a wide pattern of pathophysiological 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-bronchoalveolar 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.


OBJECTIVE
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.


CONCLUSIONS
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.
Westergren-Thorsson
Gunilla
G
Department of Experimental Medical Science, Lund University BMC D12, Lund, Sweden. gunilla.westergren-thorsson@med.lu.se
Larsen
Kristoffer
K
Nihlberg
Kristian
K
Andersson-Sjöland
Annika
A
Hallgren
Oskar
O
Marko-Varga
György
G
Bjermer
Leif
L
D056151:Airway Remodeling; D005355:Fibrosis; D006801:Humans; D007249:Inflammation / Q000473:pathology*