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NADPH Oxidases and Aging Models of Lung Fibrosis

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Book cover NADPH Oxidases

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1982))

Abstract

There is a growing recognition that aging is a risk factor for fibrosis that affects a number of organ systems, including the lung. Despite this understanding, most studies of experimental fibrosis have been conducted in young mice that typically resolve injury-induced lung fibrosis over the course of several months. Our studies demonstrate that aged mouse models may recapitulate human disease by generating a more persistent fibrotic response to injury. This is, in part, due to an imbalance in the expression and activity of NADPH oxidase (NOX) enzymes, in particular the NOX4 isoform, and a related deficiency in antioxidant responses in pathogenic myofibroblasts. These pathogenic myofibroblasts acquire features of cellular senescence and become resistant to apoptosis. In this chapter, we present methods and procedures to apply the aging model of lung fibrosis in mice that will allow interrogation of myofibroblast functions and the expression and activity of NOX4 in cells. We provide recommendations for best laboratory practices to assess the severity and resolution of fibrosis in murine models of aging.

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Acknowledgments

This work was supported by grants from the National Institute of Health: P01 HL114470 and R01 AG046210 (to VJT).

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Authors and Affiliations

  1. Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA

    Karen Bernard & Victor J. Thannickal

Authors
  1. Karen Bernard
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  2. Victor J. Thannickal
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Corresponding author

Correspondence to Victor J. Thannickal .

Editor information

Editors and Affiliations

  1. Conway Institute, School of Medicine, University College Dublin, Dublin, Ireland

    Ulla G. Knaus

  2. Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA

    Thomas L. Leto

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Bernard, K., Thannickal, V.J. (2019). NADPH Oxidases and Aging Models of Lung Fibrosis. In: Knaus, U., Leto, T. (eds) NADPH Oxidases. Methods in Molecular Biology, vol 1982. Humana, New York, NY. https://doi.org/10.1007/978-1-4939-9424-3_29

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  • DOI: https://doi.org/10.1007/978-1-4939-9424-3_29

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  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-4939-9423-6

  • Online ISBN: 978-1-4939-9424-3

  • eBook Packages: Springer Protocols

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