Early Pulmonary Fibrosis-like Changes in the Setting of Heat Exposure: DNA Damage and Cell Senescence
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...
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MDPI AG
2024-03-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/25/5/2992 |
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| author | Tong Hou Jiyang Zhang Yindan Wang Guoqing Zhang Sanduo Li Wenjun Fan Ran Li Qinghua Sun Cuiqing Liu |
| author_facet | Tong Hou Jiyang Zhang Yindan Wang Guoqing Zhang Sanduo Li Wenjun Fan Ran Li Qinghua Sun Cuiqing Liu |
| author_sort | Tong Hou |
| collection | DOAJ |
| description | 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 °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-β1 (TGF-β1) and Fibronectin (Fn1) (<i>p</i> < 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 (<i>p</i> < 0.05). Subsequently, cell senescence examination revealed that the levels of both senescence-associated β-galactosidase (SA-β-gal) staining and the cell cycle protein kinase inhibitor p21 were significantly elevated (<i>p</i> < 0.05). Mechanistically, the cGAS–STING signaling pathway evoked by DNA damage was activated in response to heat exposure (<i>p</i> < 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. |
| first_indexed | 2024-04-25T00:28:11Z |
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| language | English |
| last_indexed | 2024-04-25T00:28:11Z |
| publishDate | 2024-03-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-c9ce4aae927f4ea5a35824b9da7accde2024-03-12T16:47:10ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672024-03-01255299210.3390/ijms25052992Early Pulmonary Fibrosis-like Changes in the Setting of Heat Exposure: DNA Damage and Cell SenescenceTong Hou0Jiyang Zhang1Yindan Wang2Guoqing Zhang3Sanduo Li4Wenjun Fan5Ran Li6Qinghua Sun7Cuiqing Liu8School of Public Health, Zhejiang Chinese Medical University, Hangzhou 310053, ChinaSchool of Public Health, Zhejiang Chinese Medical University, Hangzhou 310053, ChinaSchool of Public Health, Zhejiang Chinese Medical University, Hangzhou 310053, ChinaSchool of Public Health, Zhejiang Chinese Medical University, Hangzhou 310053, ChinaSchool of Public Health, Zhejiang Chinese Medical University, Hangzhou 310053, ChinaSchool of Public Health, Zhejiang Chinese Medical University, Hangzhou 310053, ChinaSchool of Public Health, Zhejiang Chinese Medical University, Hangzhou 310053, ChinaSchool of Public Health, Zhejiang Chinese Medical University, Hangzhou 310053, ChinaSchool of Public Health, Zhejiang Chinese Medical University, Hangzhou 310053, ChinaIt 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 °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-β1 (TGF-β1) and Fibronectin (Fn1) (<i>p</i> < 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 (<i>p</i> < 0.05). Subsequently, cell senescence examination revealed that the levels of both senescence-associated β-galactosidase (SA-β-gal) staining and the cell cycle protein kinase inhibitor p21 were significantly elevated (<i>p</i> < 0.05). Mechanistically, the cGAS–STING signaling pathway evoked by DNA damage was activated in response to heat exposure (<i>p</i> < 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.https://www.mdpi.com/1422-0067/25/5/2992heat exposurelung fibrosisDNA damagesenescencecGAS–STING pathway |
| spellingShingle | Tong Hou Jiyang Zhang Yindan Wang Guoqing Zhang Sanduo Li Wenjun Fan Ran Li Qinghua Sun Cuiqing Liu Early Pulmonary Fibrosis-like Changes in the Setting of Heat Exposure: DNA Damage and Cell Senescence International Journal of Molecular Sciences heat exposure lung fibrosis DNA damage senescence cGAS–STING pathway |
| title | Early Pulmonary Fibrosis-like Changes in the Setting of Heat Exposure: DNA Damage and Cell Senescence |
| title_full | Early Pulmonary Fibrosis-like Changes in the Setting of Heat Exposure: DNA Damage and Cell Senescence |
| title_fullStr | Early Pulmonary Fibrosis-like Changes in the Setting of Heat Exposure: DNA Damage and Cell Senescence |
| title_full_unstemmed | Early Pulmonary Fibrosis-like Changes in the Setting of Heat Exposure: DNA Damage and Cell Senescence |
| title_short | Early Pulmonary Fibrosis-like Changes in the Setting of Heat Exposure: DNA Damage and Cell Senescence |
| title_sort | early pulmonary fibrosis like changes in the setting of heat exposure dna damage and cell senescence |
| topic | heat exposure lung fibrosis DNA damage senescence cGAS–STING pathway |
| url | https://www.mdpi.com/1422-0067/25/5/2992 |
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