ArticleFrontiers in immunology2024
Whole transcriptome landscape in HAPE under the stress of environment at high altitudes: new insights into the mechanisms of hypobaric hypoxia tolerance.
Article in Frontiers in immunology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- Integrated Cytokine and Immune Cell Profiling Reveals a Distinct Immune Signature Associated with High-Altitude Pulmonary Edema.International journal of molecular sciences · 2026Article
- Transcriptomic landscape of human circular RNAs: unveiling molecular mechanisms in high-altitude adaptation.Frontiers in genetics · 2026Article
- Transcriptomic analysis and experimental verification reveal the involvement of PI3K/AKT signaling pathway in high-altitude cognitive dysfunction.Frontiers in physiology · 2026Article
- Hypobaric hypoxia can lead to an increase in lung dendritic cells and promote T-cell immunosuppression, thereby preventing the excessive progression of high-altitude pulmonary edema.Frontiers in immunology · 2026Article
- Integrative blood profiling uncovers inflammatory network signatures in high-altitude pulmonary edema.Bioscience reports · 2025Article
- Dynamic human admixture histories over the past ~1300 years at the northern Himalayan frontier.Science advances · 2025Article
- N4BP3 Activates TLR4-NF-κB Pathway in Inflammatory Bowel Disease by Promoting K48-Linked IκBα Ubiquitination.Journal of inflammation research · 2025Article
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Authors and funding
6 authors.
Funding
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Abstract
Background: High altitude pulmonary edema (HAPE) is an idiopathic, noncardiogenic form of pulmonary edema that occurs at high altitudes. It is characterized by a severe clinical course and carries a significant mortality risk. Despite its clinical relevance, the molecular mechanisms underlying HAPE are not well understood. Methods: We conducted whole-transcriptome RNA sequencing on blood samples from 6 pairs of HAPE patients and healthy controls to identify differentially expressed (DE) mRNAs, miRNAs, circRNAs, lncRNAs, along with alternative splicing (AS) events, gene fusions, and novel transcripts. To explore the regulatory dynamics, we constructed ceRNA networks and analyzed immune cell infiltration patterns, further annotating the biological functions of these transcripts. For empirical validation, we selected five circRNAs from the ceRNA network and conducted RT-qPCR on 50 paired samples. Additionally, we assessed the correlations between circRNA expression levels and clinical data to evaluate their diagnostic potential. Results: We observed 2,023 differentially expressed mRNAs (DEmRNAs), 84 DEmiRNAs, 200 DEcircRNAs, and 3,573 DElncRNAs. A total of 139 'A3SS' events, 103 'A5SS' events, 545 'MXE' events, 14 'RI' events, and 1,482 'SE' events were identified in the AS events analysis between the two groups. Two ceRNA networks were constructed. T cells, follicular helper, and Macrophages M1 cells exhibited the strongest positive correlation (R=0.82), while naive B cells and memory B cells demonstrated the strongest negative correlation (R=-0.62). In total, the expression of three circRNAs was significantly different in a larger cohort. Hsa_circ_0058497, hsa_circ_0081006, and hsa_circ_0083220 demonstrated consistent with the RNA sequencing results. These three circRNAs strongly correlate with clinical indicators and exhibit potential as diagnostic biomarkers. Finally, we verified five genes (CXCR4, HSD17B2, ANGPTL4, TIMP3, N4BP3) that were differentially expressed in endothelial cells under normoxia and hypoxia through bioinformatics and RT-qPCR analyses. Conclusion: This study elucidates the differential expression of coding and non-coding RNAs (ncRNAs) in HAPE, identifies new transcripts and genes, and enhances our understanding of the transcriptional characteristics of HAPE. Moreover, it highlights the potential role of circRNAs in advancing the diagnosis and treatment of HAPE.
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