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Translating Basic Research Into Clinical Practice |

New Mechanisms of Pulmonary Fibrosis

Robert M. Strieter, MD; Borna Mehrad, MD
Author and Funding Information

Affiliations: From the Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of Virginia School of Medicine, Charlottesville, VA.

Correspondence to: Robert M. Strieter, MD, University of Virginia, Department of Medicine, Division of Pulmonary Critical Care, Box 800466, Charlottesville, VA 22908-0466; e-mail: Strieter@Virginia.edu


Funding/Support:National Institutes of Health grants CA87879 and HL66027.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal.org/site/misc/reprints.xhtml).


© 2009 American College of Chest Physicians


Chest. 2009;136(5):1364-1370. doi:10.1378/chest.09-0510
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The understanding of the pathogenesis of pulmonary fibrosis continues to evolve. The initial hypothetical model suggested chronic inflammation as the cause of pulmonary fibrosis, whereas a subsequent hypothesis posited epithelial injury and impaired wound repair as the etiology of fibrosis without preceding inflammation. Over the past decade, several concepts have led to refinement of these hypotheses. These include the following: (1) the importance of the integrity of the alveolar-capillary barrier basement membrane (BM) to conserving the architecture of the injured lung; (2) conversely, that the failure of reepithelialization and reendothelialization of this BM results in pathologic fibrosis; (3) transforming growth factor-β is necessary but not sufficient to the pathologic fibrosis of the lungs; (4) the role of persistent antigens in the pathogenesis of usual interstitial pneumonia; and (5) the contribution of epithelial-to-mesenchymal transformation and bone marrow-derived progenitor cells in the pathogenesis of lung fibrosis. In this review, we will discuss these evolving conceptual mechanisms for the pathogenesis of pulmonary fibrosis relevant to idiopathic pulmonary fibrosis.

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