Overexpression of the transcription factor GATA-3 enhances the development of pulmonary fibrosis
Open accessAbstract
Recent studies have demonstrated that Th2 cytokines, such as interleukin-4 and interleukin-13, enhance fibrotic processes by activating fibroblast proliferation and collagen production, whereas interferon-gamma, a Th1 cytokine, inhibits these processes. Th1 and Th2 cells both differentiate from common T precursor cells, with transcription factor GATA-3 a key regulator of Th2 differentiation. In the present study, therefore, we examined the effects of GATA-3 overexpression on the development of pulmonary fibrosis in a mouse model. Wild-type C57BL/6 mice and GATA-3-overexpressing (GATA-3-tg) mice of the same background were intratracheally treated with bleomycin. The survival rate after bleomycin was significantly decreased in GATA-3-tg mice compared with wild-type mice. The degree of pulmonary fibrosis was much greater in GATA-3-tg mice than in wild-type mice 28 days after bleomycin treatment. Lung interferon-gamma concentration was significantly decreased in GATA-3-tg mice compared with wild-type mice by 7 days after either saline or bleomycin treatment. The concentration of transforming growth factor-beta, a fibrogenic cytokine, was significantly higher in GATA-3-tg mice than in wild-type mice. Exogenous administration of interferon-gamma to GATA-3-tg mice improved the degree of pulmonary fibrosis and thus increased survival. These results indicate that overexpression of GATA-3 enhances the development of pulmonary fibrosis, possibly by reducing interferon-gamma levels in the lung.
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Detection of Th2 cells and their secretory mediators is enhanced in the lungs and blood of patients with IPF.
“detection of Th2 cells and their secretory mediators appears to be enhanced in the lungs and blood of patients with IPF (137–140).”
From The Role of Immune and Inflammatory Cells in Idiopathic Pulmonary Fibrosis (2018) · cites this paper as [140]
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- Authors
- Kimura, T., Ishii, Y., Yoh, K., Morishima, Y., Iizuka, T., Kiwamoto, T., Matsuno, Y., Homma, S., Nomura, A., Sakamoto, T., Takahashi, S., & Sekizawa, K.
- Affiliations
- University of Tsukuba (JP)
- Corresponding author
- Ishii, Yukio
- ORCID
- Venue
- The American Journal of Pathology
- Publisher
- Elsevier BV
- Published
- 2006-07
- Volume
- 169
- Issue
- 1
- Pages
- 96-104
- ISSN
- 0002-9440 (ISSN-L)
- PMC
- PMC1698754
- OpenAlex
- W2038838786
- Cited by
- 55
- References
- 55
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 4 · 2023: 6 · 2022: 4 · 2021: 1 · 2019: 3 · 2018: 2 · 2017: 2 · 2016: 4 · 2015: 2 · 2014: 2 · 2012: 3
- FWCI
- 2.96
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- American Journal Of Pathology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Education, Culture, Sports, Science and Technology
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Health Sciences › Medicine › Surgery › Transplantation: Methods and Outcomes
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Pulmonary Hypertension Research and Treatments
- Keywords
- GATA3, pulmonary fibrosis, Th2 differentiation, interferon-gamma, TGF-beta, bleomycin-induced lung injury, Th1/Th2 balance, transcription factor overexpression, survival
- MeSH terms
- Animals, Antimetabolites, Antineoplastic, Bleomycin, Bronchoalveolar Lavage Fluid, Flow Cytometry, Interferon-gamma, Mice, Transgenic, Pulmonary Fibrosis, CD4-Positive T-Lymphocytes, Transforming Growth Factor beta, GATA3 Transcription Factor, Mice
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