{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T04:32:53Z","timestamp":1780633973992,"version":"3.54.1"},"reference-count":43,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2025,8,15]],"date-time":"2025-08-15T00:00:00Z","timestamp":1755216000000},"content-version":"vor","delay-in-days":226,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"The President\u2019s Foundation of The Third Affiliated Hospital of Southern Medical University","award":["NO.YM202204; NO.YM202207; NO.YQ202211"],"award-info":[{"award-number":["NO.YM202204; NO.YM202207; NO.YQ202211"]}]},{"name":"Guangdong Medical Science and Technology Research Fund Project","award":["NO. A2024430"],"award-info":[{"award-number":["NO. A2024430"]}]},{"name":"the National Nature Science Fund of China","award":["NO.81901997"],"award-info":[{"award-number":["NO.81901997"]}]},{"name":"the Natural Science Foundation of Guangdong Province","award":["NO.2024A1515030283; NO.2022A1515012350; NO.2020A1515010092; NO.2019A1515010295"],"award-info":[{"award-number":["NO.2024A1515030283; NO.2022A1515012350; NO.2020A1515010092; NO.2019A1515010295"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,1,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>The high mortality rate of severe heat stroke is mainly related to multiple organ dysfunction syndrome (MODS), and respiratory failure caused by acute lung injury (ALI) is a significant factor in the development of MODS during the course of severe heat stroke. Previous research has demonstrated that severe heat stroke-induced acute lung injury (sHS-ALI) is associated with an increase in reactive oxygen species (ROS) in vascular endothelial cells (VECs), but the specific initiating factors and intermediate mechanisms involved are unclear.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>In this study, the mRNA profiles of mouse lung tissues were analysed using high-throughput sequencing. Genome-wide knockout was performed using CRISPR-Cas9 technology to identify a cohort of differentially expressed genes that promote human umbilical vein endothelial cells survival after heat stress. The expression of key proteins [fibroblast growth factor 23 (FGF23), phosphorylated fibroblast growth factor receptor-1 (p-FGFR-1), FGFR-1, phosphorylated phospholipase C-\u03b32 (p-PLC-\u03b32), PLC-\u03b32, p\u2013p47phox, p67phox, p22phox, p40phox, and nicotinamide adenine dinucleotide phosphate oxidase isoform 2 (NOX2)] involved in the FGF23\/FGFR-1 mechanism was examined using western blotting and immunohistochemistry.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>In this study, we first screened sHS-ALI target genes by cross-comparison in vivo and in vitro and found that FGF23 is the upstream promoter of sHS-ALI. Subsequent investigations involving the interference or inhibition of FGF23 expression revealed that FGF23 induced FGFR-1 Y766 phosphorylation during heat stress-induced VECs damage. In addition, FGF23 participated in NOX2 activation and ROS accumulation and was involved in the process of sHS-ALI. These findings indicated that the FGFR-1 Y766 site mutation strongly suppressed the production of p-PLC-\u03b32 and heat stress-induced NOX2-ROS activation in VECs. More importantly, mutation of the FGFR-1 Y766 phosphorylation site had no effect on FGF23 expression, and it was impossible to significantly induce the expression of p-PLC-\u03b32. Moreover, NOX2-ROS activation was inhibited, even in the presence of heat stress, the recombinant FGF23 protein, or combined stimulation.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>This study confirmed that FGF23\/FGFR1 signalling, as an upstream priming factor, mediated NOX2-ROS activation in VECs after heat stress, thus participating in the sHS-ALI process. FGFR-1 Y766 phosphorylation is essential for FGF23\/FGFR-1 signalling activation in VECs, which is involved in sHS-ALI. These findings further clarify the mechanism underlying sHS-ALI and contribute to reducing the mortality and morbidity of severe heat stroke.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/burnst\/tkae050","type":"journal-article","created":{"date-parts":[[2024,7,26]],"date-time":"2024-07-26T18:52:04Z","timestamp":1722019924000},"source":"Crossref","is-referenced-by-count":4,"title":["The mechanism by which FGF23\/FGFR-1 activates NOX2-ROS in vascular endothelial cells in the context of severe heat stroke-induced acute lung injury"],"prefix":"10.1093","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8566-6634","authenticated-orcid":false,"given":"Zhengtao","family":"Gu","sequence":"first","affiliation":[{"name":"Department of Traumatic Orthopaedics, The Second Affiliated Hospital, Guangzhou Medical University , No. 250, Changgang East Road, Haizhu District, Guangzhou, 510120, Guangdong 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, No. 183, Zhongshan Avenue West, Tianhe District, Guangzhou, 510063, Guangdong ,","place":["China"]},{"name":"Academy of Orthopedics \u00b7 Guangdong Province, Orthopedic Hospital of Guangdong Province, Guangdong Provincial Key Laboratory of Bone and Joint Degenerative Diseases, The Third Affiliated Hospital, Southern Medical University , No. 295, Changxing Road, Tianhe District, Guangzhou, 510650, Guangdong ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-3601-6870","authenticated-orcid":false,"given":"Jian","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Treatment Center For Traumatic Injuries, The Third Affiliated Hospital, Southern Medical University , No. 183, Zhongshan Avenue West, Tianhe District, Guangzhou, 510063, Guangdong ,","place":["China"]},{"name":"Academy of Orthopedics \u00b7 Guangdong Province, Orthopedic Hospital of Guangdong Province, Guangdong Provincial Key Laboratory 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