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DOI10.3390/ijms25052992
Early Pulmonary Fibrosis-like Changes in the Setting of Heat Exposure: DNA Damage and Cell Senescence
发表日期2024
ISSN1661-6596
EISSN1422-0067
起始页码25
结束页码5
卷号25期号:5
英文摘要It is well known that extreme heat events happen frequently due to climate change. However, studies examining the direct health impacts of increased temperature and heat waves are lacking. Previous reports revealed that heatstroke induced acute lung injury and pulmonary dysfunction. This study aimed to investigate whether heat exposure induced lung fibrosis and to explore the underlying mechanisms. Male C57BL/6 mice were exposed to an ambient temperature of 39.5 +/- 0.5 degrees C until their core temperature reached the maximum or heat exhaustion state. Lung fibrosis was observed in the lungs of heat-exposed mice, with extensive collagen deposition and the elevated expression of fibrosis molecules, including transforming growth factor-beta 1 (TGF-beta 1) and Fibronectin (Fn1) (p < 0.05). Moreover, epithelial-mesenchymal transition (EMT) occurred in response to heat exposure, evidenced by E-cadherin, an epithelial marker, which was downregulated, whereas markers of EMT, such as connective tissue growth factor (CTGF) and the zinc finger transcriptional repressor protein Slug, were upregulated in the heat-exposed lung tissues of mice (p < 0.05). Subsequently, cell senescence examination revealed that the levels of both senescence-associated beta-galactosidase (SA-beta-gal) staining and the cell cycle protein kinase inhibitor p21 were significantly elevated (p < 0.05). Mechanistically, the cGAS-STING signaling pathway evoked by DNA damage was activated in response to heat exposure (p < 0.05). In summary, we reported a new finding that heat exposure contributed to the development of early pulmonary fibrosis-like changes through the DNA damage-activated cGAS-STING pathway followed by cellular senescence.
英文关键词heat exposure; lung fibrosis; DNA damage; senescence; cGAS-STING pathway
语种英语
WOS研究方向Biochemistry & Molecular Biology ; Chemistry
WOS类目Biochemistry & Molecular Biology ; Chemistry, Multidisciplinary
WOS记录号WOS:001183329800001
来源期刊INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
文献类型期刊论文
条目标识符http://gcip.llas.ac.cn/handle/2XKMVOVA/301173
作者单位Zhejiang Chinese Medical University
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. Early Pulmonary Fibrosis-like Changes in the Setting of Heat Exposure: DNA Damage and Cell Senescence[J],2024,25(5).
APA (2024).Early Pulmonary Fibrosis-like Changes in the Setting of Heat Exposure: DNA Damage and Cell Senescence.INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES,25(5).
MLA "Early Pulmonary Fibrosis-like Changes in the Setting of Heat Exposure: DNA Damage and Cell Senescence".INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 25.5(2024).
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