{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T05:33:13Z","timestamp":1793251993943,"version":"4.5.0"},"reference-count":52,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T00:00:00Z","timestamp":1779408000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>High-altitude cerebral edema (HACE) is a life-threatening condition following rapid ascent to high altitude, with acute mountain sickness (AMS) as a key precursor. Increasing evidence implicates inflammation in its pathogenesis, yet the molecular regulatory networks remain unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We integrated bulk RNA-seq (GSE75665), non-coding RNA-seq (GSE90500), and single-cell RNA-seq datasets to explore inflammation-related mechanisms in AMS. Differentially expressed genes (DEGs) were identified and analyzed using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA). Protein-protein interaction, miRNA-mRNA, transcription factor, and drug-gene networks were constructed. Single-cell and deconvolution analyses determined cell-type-specific expression and immune composition. A hypobaric hypoxia-induced HACE mouse model was established for experimental validation to assess heparin-binding EGF-like growth factor (HBEGF) expression and associated neuroinflammatory and pathological changes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We identified 323 DEGs, including five 5 inflammation-related genes, all downregulated in AMS and enriched in epithelial cell growth, migration, and the ErbB signaling pathway. hsa-miR-375 was predicted to regulate multiple key genes, and drug gene analysis highlighted HBEGF as a potential therapeutic target. Single-cell data revealed monocytes as the major source of key gene expression and increased CD4\n                      <jats:sup>+<\/jats:sup>\n                      monocytes in AMS.\n                      <jats:italic>In vivo<\/jats:italic>\n                      , HBEGF expression was significantly reduced in HACE mice, while Adeno-associated virus (AAV)-mediated HBEGF overexpression mitigated cerebral edema, blood-brain barrier disruption, neuronal injury, and proinflammatory cytokine release.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This integrative multi-omics study identifies monocyte-mediated inflammation and the ErbB pathway as critical mechanisms in HACE. HBEGF emerges as a promising therapeutic target for preventing neuroinflammation and cerebral injury in high-altitude conditions.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1745433","type":"journal-article","created":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T11:22:33Z","timestamp":1779448953000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Integrative multi-omics analysis reveals inflammation-related molecular networks in acute mountain sickness"],"prefix":"10.3389","volume":"17","author":[{"given":"Zhicheng","family":"Xiang","sequence":"first","affiliation":[{"name":"College of Clinical Medicine Qinghai University","place":["Xining, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haifeng","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Qinghai Provincial People\u2019s Hospital","place":["Xining, 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