Stat-3 is required for pulmonary homeostasis during hyperoxia
Open accessAbstract
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.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Respiratory epithelium-specific STAT3 knockout impairs injury tolerance.
“Impaired injury tolerance”
From Targeting Janus Kinases and Signal Transducer and Activator of Transcription 3 To Treat Inflammation, Fibrosis, and Cancer: Rationale, Progress, and Caution (2020) · cites this paper as Hokuto et al., 2004
Respiratory epithelial cell-specific STAT3-KO mice progress more rapidly than STAT3 wild-type mice to lung injury after exposure to 95% oxygen, indicating a hyperoxia-protective role for STAT3.
“Respiratory epithelial cell–specific STAT3-KO mice progressed more rapidly than STAT3 wild-type mice to lung injury after exposure to 95% oxygen (Hokuto et al., 2004), indicating a hyperoxia-protective role for STAT3.”
From Targeting Janus Kinases and Signal Transducer and Activator of Transcription 3 To Treat Inflammation, Fibrosis, and Cancer: Rationale, Progress, and Caution (2020) · cites this paper as Hokuto et al., 2004
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Takeda, K., Kaisho, T., Yoshida, N., Takeda, J., Kishimoto, T., & Akira, S. (1998) · The Journal of Immunology · doi:10.4049/jimmunol.161.9.4652 · Cited by 584 · see citing works
Self-citation
Flagged first, then by citations
Research works printed but not linked: 7
- Takeda, K., et al. 1997. Targeted disruption of the mouse Stat3 gene leads to early embryonic lethality. Proc. Natl. Acad. Sci. U. S. A. 94:3801-3804.
- Levy, D.E., and Lee, C.K. 2002. What does Stat3 do? J. Clin. Invest. 109:1143-1148. doi:10.1172/JCI200215650. · DOI
- Clark, J.C., et al. 1995. Targeted disruption of the surfactant protein B gene disrupts surfactant homeostasis, causing respiratory failure in newborn mice. Proc. Natl. Acad. Sci. U. S. A. 92:7794-7798.
- Perl, A.K., Wert, S.E., Nagy, A., Lobe, C.G., and Whitsett, J.A. 2002. Early restriction of peripheral and proximal cell lineages during formation of the lung. Proc. Natl. Acad. Sci. U. S. A. 99:10482-10487.
- Schuessler, T.F., and Bates, J.H. 1995. A computer-controlled research ventilator for small animals: design and evaluation. IEEE Trans. Biomed. Eng. 42:860-866.
- Glasser, S.W., et al. 2001. Altered stability of pulmonary surfactant in SP-C-deficient mice. Proc. Natl. Acad. Sci. U. S. A. 98:6366-6371.
- Korfhagen, T.R., et al. 1996. Altered surfactant function and structure in SP-A gene targeted mice. Proc. Natl. Acad. Sci. U. S. A. 93:9594-9599.
Cited by
Sorted by citations
Bharadwaj, U., Kasembeli, M. M., Robinson, P., & Tweardy, D. J. (2020) · Pharmacological Reviews · doi:10.1124/pr.119.018440 · Cited by 314 · see citing works
rtTA toxicity limits the usefulness of the SP-C-rtTA transgenic mouse
Morimoto, M., & Kopan, R. (2009) · Developmental Biology · doi:10.1016/j.ydbio.2008.10.013 · Cited by 62 · see citing works
- Authors
- Hokuto, I., Ikegami, M., Yoshida, M., Takeda, K., Akira, S., Perl, A.-K. T., Hull, W. M., Wert, S. E., & Whitsett, J. A.
- Affiliations
- Cincinnati Children's Hospital Medical Center (US)
- Research Institute for Microbial Diseases, The University of Osaka (JP)
- Corresponding author
- Whitsett, Jeffrey A.
- ORCID
- Venue
- Journal of Clinical Investigation
- Published
- 2004-01-01
- Volume
- 113
- Issue
- 1
- Pages
- 28-37
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC300770
- OpenAlex
- W2114176892
- Cited by
- 128
- References
- 1
- Citations by year
- 2025: 6 · 2024: 1 · 2023: 4 · 2022: 4 · 2021: 4 · 2020: 4 · 2019: 2 · 2018: 4 · 2017: 4 · 2016: 2 · 2015: 4 · 2014: 6 · 2013: 3 · 2012: 8
- FWCI
- 10.52
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (HL61646)
- National Heart, Lung, and Blood Institute (R01HL038859, HL-38859, HL-61646, P01HL061646, R37HL038859)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Neonatal Respiratory Health Research
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Respiratory Support and Mechanisms
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Keywords
- STAT3, hyperoxia, acute lung injury, pulmonary homeostasis, airway epithelial cells, surfactant protein C, conditional gene deletion, surfactant homeostasis, surfactant protein B, acute respiratory distress syndrome, epithelial damage, inflammation, lung morphogenesis
- MeSH terms
- Adult, Animals, Hypoxia, Base Sequence, Child, DNA-Binding Proteins, Humans, Immunohistochemistry, Lung, Lung Diseases, Mice, Transgenic, RNA, Messenger, Transcription, Genetic, Trans-Activators, Polymerase Chain Reaction, DNA Primers, Mice, Knockout, Respiratory Mucosa, Pulmonary Surfactant-Associated Protein B, STAT3 Transcription Factor, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
