NADPH Oxidases pp 487-496 | Cite as

NADPH Oxidases and Aging Models of Lung Fibrosis

  • Karen Bernard
  • Victor J. ThannickalEmail author
Part of the Methods in Molecular Biology book series (MIMB, volume 1982)


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.

Key words

NADPH oxidase Fibrosis Myofibroblasts NOX4 Bleomycin injury Aging Oxidative stress 



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


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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Division of Pulmonary, Allergy and Critical Care Medicine, Department of MedicineUniversity of Alabama at BirminghamBirminghamUSA

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