PT  - JOURNAL ARTICLE
AU  - D. Abraham
TI  - Role of endothelin in lung fibrosis
AID  - 10.1183/09059180.00010907
DP  - 2008 Dec 01
TA  - European Respiratory Review
PG  - 145--150
VI  - 17
IP  - 109
4099  - http://err.ersjournals.com/content/17/109/145.short
4100  - http://err.ersjournals.com/content/17/109/145.full
SO  - EUROPEAN RESPIRATORY REVIEW2008 Dec 01; 17
AB  - Accumulating evidence suggests that idiopathic pulmonary fibrosis (IPF) results from lung injury primarily following an abnormal wound healing response towards epithelial cell damage. Thus, rather than resulting from chronic inflammation, as thought previously, the inflammatory response acts as a modifier of the fibrogenic response, which can also be influenced by the host’s genetic background and environmental triggers. Several key mediators, including endothelin (ET)-1, have been implicated in the fibrosis and scarring associated with IPF. Elevated levels of ET-1 have been detected in bronchoalveolar lavage fluid and serum from patients with IPF and increased expression of ET-1 has been detected in small pulmonary blood vessels and macrophages. In vitro data show that ET-1 influences matrix production and degradation by promoting synthesis of collagen type I and III, inhibiting expression of matrix metalloproteinase-1 and promoting matrix remodelling. In addition, ET-1 promotes fibroblast differentiation to a myofibroblastic cell type, inducing the expression of proteins that contribute to a contractile phenotype including α-smooth muscle actin. Moreover, ET-1 has been shown to initiate alveolar epithelial cell transition into fibroblast-like cells, a process termed epithelial–mesenchymal transition, and thereby contribute to pulmonary fibrosis. Furthermore, recently reported data from the BUILD (Bosentan Use in Interstitial Lung Disease)-1 trial showed a trend towards a delay in time to disease progression or death following treatment with the endothelin receptor antagonist, bosentan, which was especially prominent in patients with biopsy-proven IPF. This adds to the evidence that ET-1 plays an important role in IPF. The present article examines recent evidence for the role of endothelin-1 in pulmonary fibrosis, and particularly, in the control of the function and differentiation of fibroblasts and myofibroblasts.