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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 \u00b1 0.5 \u00b0C 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-\u03b21 (TGF-\u03b21) and Fibronectin (Fn1) (p &lt; 0.05). Moreover, epithelial\u2013mesenchymal 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 &lt; 0.05). Subsequently, cell senescence examination revealed that the levels of both senescence-associated \u03b2-galactosidase (SA-\u03b2-gal) staining and the cell cycle protein kinase inhibitor p21 were significantly elevated (p &lt; 0.05). Mechanistically, the cGAS\u2013STING signaling pathway evoked by DNA damage was activated in response to heat exposure (p &lt; 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\u2013STING pathway followed by cellular senescence.<\/jats:p>","DOI":"10.3390\/ijms25052992","type":"journal-article","created":{"date-parts":[[2024,3,5]],"date-time":"2024-03-05T03:03:20Z","timestamp":1709607800000},"page":"2992","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Early Pulmonary Fibrosis-like Changes in the Setting of Heat Exposure: DNA Damage and Cell Senescence"],"prefix":"10.3390","volume":"25","author":[{"given":"Tong","family":"Hou","sequence":"first","affiliation":[{"name":"School of Public Health, Zhejiang Chinese Medical University, Hangzhou 310053, China"},{"name":"Zhejiang International Science and Technology Cooperation Base of Air Pollution and Health, Hangzhou 310053, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiyang","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Public Health, Zhejiang Chinese Medical University, Hangzhou 310053, China"},{"name":"Zhejiang International Science and Technology Cooperation Base of Air Pollution and Health, Hangzhou 310053, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yindan","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Public Health, Zhejiang Chinese Medical University, Hangzhou 310053, China"},{"name":"Zhejiang International Science and Technology Cooperation Base of Air Pollution and Health, Hangzhou 310053, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoqing","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Public Health, Zhejiang Chinese Medical University, Hangzhou 310053, China"},{"name":"Zhejiang International Science and Technology Cooperation Base of Air Pollution and Health, Hangzhou 310053, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanduo","family":"Li","sequence":"additional","affiliation":[{"name":"School of Public Health, Zhejiang Chinese Medical University, Hangzhou 310053, China"},{"name":"Zhejiang International Science and Technology Cooperation Base of Air Pollution and Health, Hangzhou 310053, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjun","family":"Fan","sequence":"additional","affiliation":[{"name":"School of Public Health, Zhejiang Chinese Medical University, Hangzhou 310053, China"},{"name":"Zhejiang International Science and Technology Cooperation Base of Air Pollution and Health, Hangzhou 310053, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ran","family":"Li","sequence":"additional","affiliation":[{"name":"School of Public Health, Zhejiang Chinese Medical University, Hangzhou 310053, China"},{"name":"Zhejiang International Science and Technology Cooperation Base of Air Pollution and Health, Hangzhou 310053, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinghua","family":"Sun","sequence":"additional","affiliation":[{"name":"School of Public Health, Zhejiang Chinese Medical University, Hangzhou 310053, China"},{"name":"Zhejiang International Science and Technology Cooperation Base of Air Pollution and Health, Hangzhou 310053, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cuiqing","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Public Health, Zhejiang Chinese Medical University, Hangzhou 310053, China"},{"name":"Zhejiang International Science and Technology Cooperation Base of Air Pollution and Health, Hangzhou 310053, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"111511","DOI":"10.1016\/j.envres.2021.111511","article-title":"Climate change and neurodegenerative diseases","volume":"201","author":"Bongioanni","year":"2021","journal-title":"Environ. 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