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Matrix Metalloproteinases and Protein Tyrosine KinasesNovel Targets in Acute Lung Injury and ARDS: Potential Novel Targets in Acute Lung Injury and ARDS

Yael Aschner, MD; Rachel L. Zemans, MD; Cory M. Yamashita, MD; Gregory P. Downey, MD, FCCP
Author and Funding Information

From the Division of Pulmonary, Critical Care, and Sleep Medicine (Drs Aschner, Zemans, and Downey), Departments of Medicine and Pediatrics, National Jewish Health, Denver, CO; Division of Pulmonary Sciences and Critical Care Medicine, Departments of Medicine (Drs Aschner, Zemans, and Downey) and Immunology (Dr Downey), University of Colorado Denver, Aurora, CO; and Department of Medicine (Dr Yamashita), University of Western Ontario, London, ON, Canada.

CORRESPONDENCE TO: Gregory Downey, MD, FCCP, Academic Affairs, K701b National Jewish Health, 1400 Jackson St, Denver, CO, 80206; e-mail: downeyg@njhealth.org


FUNDING/SUPPORT: This review was supported by funding from the National Institutes of Health [HL103772 (R. L. Z.) and HL090669 (G. P. D.)].

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2014;146(4):1081-1091. doi:10.1378/chest.14-0397
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Acute lung injury (ALI) and ARDS fall within a spectrum of pulmonary disease that is characterized by hypoxemia, noncardiogenic pulmonary edema, and dysregulated and excessive inflammation. While mortality rates have improved with the advent of specialized ICUs and lung protective mechanical ventilation strategies, few other therapies have proven effective in the management of ARDS, which remains a significant clinical problem. Further development of biomarkers of disease severity, response to therapy, and prognosis is urgently needed. Several novel pathways have been identified and studied with respect to the pathogenesis of ALI and ARDS that show promise in bridging some of these gaps. This review will focus on the roles of matrix metalloproteinases and protein tyrosine kinases in the pathobiology of ALI in humans, and in animal models and in vitro studies. These molecules can act independently, as well as coordinately, in a feed-forward manner via activation of tyrosine kinase-regulated pathways that are pivotal in the development of ARDS. Specific signaling events involving proteolytic processing by matrix metalloproteinases that contribute to ALI, including cytokine and chemokine activation and release, neutrophil recruitment, transmigration and activation, and disruption of the intact alveolar-capillary barrier, will be explored in the context of these novel molecular pathways.

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