Proteasomal regulation of pulmonary fibrosis
It is estimated that, combined, 400,000 people are diagnosed with idiopathic pulmonary fibrosis (IPF) or acute lung injury/acute respiratory distress syndrome annually in the United States, and both diseases are associated with an unacceptably high mortality rate. Although these disorders are distin...
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Published in | Proceedings of the American Thoracic Society Vol. 7; no. 1; pp. 77 - 83 |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
United States
American Thoracic Society
15.02.2010
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Subjects | |
Online Access | Get full text |
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Summary: | It is estimated that, combined, 400,000 people are diagnosed with idiopathic pulmonary fibrosis (IPF) or acute lung injury/acute respiratory distress syndrome annually in the United States, and both diseases are associated with an unacceptably high mortality rate. Although these disorders are distinct clinical entities, they share pathogenic mechanisms that may provide overlapping therapeutic targets. One example is fibroblast activation, which occurs concomitant with acute lung injury as well as in the progressive fibrosis of IPF. Both clinical entities are characterized by elevations of the profibrotic cytokine, transforming growth factor (TGF)-beta1. Protein degradation by the ubiquitin-proteasomal system modulates TGF-beta1 expression and signaling. In this review, we highlight the effects of proteasomal inhibition in various animal models of tissue fibrosis and mechanisms by which it may regulate TGF-beta1 expression and signaling. At present, there are no effective therapies for fibroproliferative acute respiratory distress syndrome or IPF, and proteasomal inhibition may provide a novel, attractive target in these devastating diseases. |
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Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-3 content type line 23 ObjectType-Review-1 Conflict of Interest Statement: C.H.W. has received funding from noncommercial entity, the National Institutes of Health ($10,001–$50,000). G.R.S.B. and G.M.M. do not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. M.J. has received funding from noncommercial entity, the Cystic Fibrosis Foundation ($50,001–$100,000). Supported by National Institutes of Health grant 5P01HL071643-05, National Heart, Lung, and Blood Institute/National Center for Research Resources grants 1K12RR017707-02 and M01 RR-00048, and by the American Lung Association, Northwestern Memorial Foundation. |
ISSN: | 1546-3222 1943-5665 |
DOI: | 10.1513/pats.200906-055JS |