Integrative multi-omics analysis reveals inflammation-related molecular networks in acute mountain sickness.
Overview
- College of Clinical Medicine Qinghai University, Xining, China
- Department of Neurosurgery, Qinghai Provincial People’s Hospital, Xining, China
- Qinghai University Affiliated Hospital, School of Clinical Medicine, Qinghai University, Xining, China
Abstract
Background: 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.
Methods: 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.
Results: 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+ monocytes in AMS. In vivo, 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.
Conclusions: 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.
Reproduced under the paper's license (CC BY), from the paper cited above.
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Data
Datasets cited
- geo:GSE75665, at NCBI GEO; found in the text, “Raw data processing and differential…”
Other data links
- ncbi.nlm.nih.gov/
geo , NCBI; found in the text, “Data sources” - ncbi.nlm.nih.gov/
sra , NCBI; found in the text, “Data sources”
Data availability statement
The datasets presented in this study can be found in online repositories. The names of the repository/
Reproduced under the paper's license (CC BY), from the paper cited above.
Versions
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Version 1, 28 September 2026: the first record
Recorded: type, language, journal, volume, pages, dates, 7 authors, 5 keywords, 13 MeSH terms, 52 references.
Cite
This paper
Xiang, Z., Ma, H., Cao, D., Zhang, F., Yang, C., Cao, T., & Zhang, Q. (2026). Integrative multi-omics analysis reveals inflammation-related molecular networks in acute mountain sickness. Frontiers in immunology, 17, 1745433. https://
BibTeX
@article{xiang2026integr
author = {Xiang, Zhicheng and Ma, Haifeng and Cao, Dahai and Zhang, Fei and Yang, Chunqing and Cao, Taijian and Zhang, Qiang},
title = {{Integrative multi-omics analysis reveals inflammation-related molecular networks in acute mountain sickness}},
journal = {Frontiers in immunology},
year = {2026},
month = may,
volume = {17},
pages = {1745433},
publisher = {Frontiers Media SA},
issn = {1664-3224},
doi = {10.3389/
url = {https://
pmid = {42254026},
pmcid = {PMC13237639}
}
RIS
TY - JOUR
AU - Xiang, Zhicheng
AU - Ma, Haifeng
AU - Cao, Dahai
AU - Zhang, Fei
AU - Yang, Chunqing
AU - Cao, Taijian
AU - Zhang, Qiang
TI - Integrative multi-omics analysis reveals inflammation-related molecular networks in acute mountain sickness
T2 - Frontiers in immunology
J2 - Front Immunol
PY - 2026
DA - 2026/
VL - 17
SP - 1745433
SN - 1664-3224
PB - Frontiers Media SA
DO - 10.3389/
UR - https://
LA - en
ER -
CSL-JSON
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