Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Alerts
  • Advertising
  • Job board
  • Subscribe
  • Contact
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Author's Takes
  • Reviews
    • View all reviews ...
    • Aging (Upcoming)
    • Next-Generation Sequencing in Medicine (Jun 2022)
    • New Therapeutic Targets in Cardiovascular Diseases (Mar 2022)
    • Immunometabolism (Jan 2022)
    • Circadian Rhythm (Oct 2021)
    • Gut-Brain Axis (Jul 2021)
    • Tumor Microenvironment (Mar 2021)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Commentaries
    • Concise Communication
    • Editorials
    • Viewpoint
    • Top read articles
  • Clinical Medicine
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Author's Takes
  • In-Press Preview
  • Commentaries
  • Concise Communication
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Alerts
  • Advertising
  • Job board
  • Subscribe
  • Contact
Stat-3 is required for pulmonary homeostasis during hyperoxia
Isamu Hokuto, … , Susan E. Wert, Jeffrey A. Whitsett
Isamu Hokuto, … , Susan E. Wert, Jeffrey A. Whitsett
Published January 1, 2004
Citation Information: J Clin Invest. 2004;113(1):28-37. https://doi.org/10.1172/JCI19491.
View: Text | PDF
Article Pulmonology

Stat-3 is required for pulmonary homeostasis during hyperoxia

  • Text
  • PDF
Abstract

Acute lung injury syndromes remain common causes of morbidity and mortality in adults and children. Cellular and physiologic mechanisms maintaining pulmonary homeostasis during lung injury remain poorly understood. In the present study, the Stat-3 gene was selectively deleted in respiratory epithelial cells by conditional expression of Cre-recombinase under control of the surfactant protein C gene promoter. Cell-selective deletion of Stat-3 in respiratory epithelial cells did not alter prenatal lung morphogenesis or postnatal lung function. However, exposure of adult Stat-3–deleted mice to 95% oxygen caused a more rapidly progressive lung injury associated with alveolar capillary leak and acute respiratory distress. Epithelial cell injury and inflammatory responses were increased in the Stat-3–deleted mice. Surfactant proteins and lipids were decreased or absent in alveolar lavage material. Intratracheal treatment with exogenous surfactant protein B improved survival and lung histology in Stat-3–deleted mice during hyperoxia. Expression of Stat-3 in respiratory epithelial cells is not required for lung formation, but plays a critical role in maintenance of surfactant homeostasis and lung function during oxygen injury.

Authors

Isamu Hokuto, Machiko Ikegami, Mitsuhiro Yoshida, Kiyoshi Takeda, Shizuo Akira, Anne-Karina T. Perl, William M. Hull, Susan E. Wert, Jeffrey A. Whitsett

×

Figure 6

Options: View larger image (or click on image) Download as PowerPoint
Increased alveolar capillary leak and decreased surfactant in Stat-3Δ/Δ ...
Increased alveolar capillary leak and decreased surfactant in Stat-3Δ/Δ mice after hyperoxia. (a) Total protein concentration was measured in lung lavage fluid 65 hours after exposure to 95% O2. Protein content was similar in control and Stat-3Δ/Δ mice in room air. After oxygen exposure, BALF protein recovered from each mouse (micrograms per kilogram) was significantly increased in the Stat-3Δ/Δ mice, n = 5 per group. *P < 0.05 versus others and P < 0.001 versus room air, as assessed by ANOVA. (b) Surfactant saturated phosphatidylcholine (SatPC) was significantly decreased in BALF from the Stat-3Δ/Δ mice following hyperoxia. Statistical differences were analyzed by ANOVA. †P < 0.001 versus air.

Copyright © 2022 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts