ArticleAmerican journal of physiology. Lung cellular and molecular physiology2015
Role of GADD45a in murine models of radiation- and bleomycin-induced lung injury.
Article in American journal of physiology. Lung cellular and molecular physiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 15 citations in OpenAlex.
- Bone Marrow Stem Cell Exosomes Protect Lung Cells from Oxygen Damage by Regulating miR-23a-3p/Slc7a2 Pathway.The journal of gene medicine · 2026Article
- Transcriptomic differences in chromatin and cell cycle regulation in A549 cells after irradiation with carbon ions and X-rays.Frontiers in oncology · 2026Article
- DNA hypomethylation-mediated upregulation of GADD45B facilitates airway inflammation and epithelial cell senescence in COPD.Journal of advanced research · 2025Article
- Growth arrest and DNA damage-inducible 45: a new player on inflammatory diseases.Frontiers in immunology · 2025Review
- Deficiency of the Deubiquitinase UCHL1 Attenuates Pulmonary Arterial Hypertension.Circulation · 2024Article
- Article
- Impact of GADD45A on Radiation Biodosimetry Using Mouse Peripheral Blood.Radiation research · 2023Article
- The spike protein of SARS-CoV-2 induces inflammation and EMT of lung epithelial cells and fibroblasts through the upregulation of GADD45A.Open medicine (Warsaw, Poland) · 2023Article
- Lung transcriptome of nonhuman primates exposed to total- and partial-body irradiation.Molecular therapy. Nucleic acids · 2022Article
- Bioinformatic identification and analysis of immune-related chromatin regulatory genes as potential biomarkers in idiopathic pulmonary fibrosis.Annals of translational medicine · 2022Article
- eNAMPT Is a Novel Damage-associated Molecular Pattern Protein That Contributes to the Severity of Radiation-induced Lung Fibrosis.American journal of respiratory cell and molecular biology · 2022Article
- A Trans-Agency Workshop on the Pathophysiology of Radiation-Induced Lung Injury.Radiation research · 2022Article
- Involvement of eNAMPT/TLR4 signaling in murine radiation pneumonitis: protection by eNAMPT neutralization.Translational research : the journal of laboratory and clinical medicine · 2022Article
- Sphingolipids as a Novel Therapeutic Target in Radiation-Induced Lung Injury.Cell biochemistry and biophysics · 2021Review
- GADD45A is a protective modifier of neurogenic skeletal muscle atrophy.JCI insight · 2021Article
- Endothelial cell signaling and ventilator-induced lung injury: molecular mechanisms, genomic analyses, and therapeutic targets.American journal of physiology. Lung cellular and molecular physiology · 2017Review
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
We previously reported protective effects of GADD45a (growth arrest and DNA damage-inducible gene 45 alpha) in murine ventilator-induced lung injury (VILI) via effects on Akt-mediated endothelial cell signaling. In the present study we investigated the role of GADD45a in separate murine models of radiation- and bleomycin-induced lung injury. Initial studies of wild-type mice subjected to single-dose thoracic radiation (10 Gy) confirmed a significant increase in lung GADD45a expression within 24 h and persistent at 6 wk. Mice deficient in GADD45a (GADD45a(-/-)) demonstrated increased susceptibility to radiation-induced lung injury (RILI, 10 Gy) evidenced by increased bronchoalveolar lavage (BAL) fluid total cell counts, protein and albumin levels, and levels of inflammatory cytokines compared with RILI-challenged wild-type animals at 2 and 4 wk. Furthermore, GADD45a(-/-) mice had decreased total and phosphorylated lung Akt levels both at baseline and 6 wk after RILI challenge relative to wild-type mice while increased RILI susceptibility was observed in both Akt(+/-) mice and mice treated with an Akt inhibitor beginning 1 wk prior to irradiation. Additionally, overexpression of a constitutively active Akt1 transgene reversed RILI-susceptibility in GADD45a(-/-) mice. In separate studies, lung fibrotic changes 2 wk after treatment with bleomycin (0.25 U/kg IT) was significantly increased in GADD45a(-/-) mice compared with wild-type mice assessed by lung collagen content and histology. These data implicate GADD45a as an important modulator of lung inflammatory responses across different injury models and highlight GADD45a-mediated signaling as a novel target in inflammatory lung injury clinically.
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