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TNF-α and RPLP0 drive the apoptosis of endothelial cells and increase susceptibility to high-altitude pulmonary edema.
Ge, Yi-Ling; Li, Pei-Jie; Bu, Ying-Rui; Zhang, Bin; Xu, Jin; He, Si-Yuan; Cao, Qing-Lin; Bai, Yun-Gang; Ma, Jin; Zhang, Lin; Zhou, Jie; Xie, Man-Jiang.
Afiliación
  • Ge YL; Department of Aerospace Physiology, Key Laboratory of Aerospace Medicine of Ministry of Education, Fourth Military Medical University, Xi'an, Shaanxi Province, 710032, China.
  • Li PJ; Department of Aerospace Physiology, Key Laboratory of Aerospace Medicine of Ministry of Education, Fourth Military Medical University, Xi'an, Shaanxi Province, 710032, China.
  • Bu YR; Department of Aerospace Physiology, Key Laboratory of Aerospace Medicine of Ministry of Education, Fourth Military Medical University, Xi'an, Shaanxi Province, 710032, China.
  • Zhang B; Department of Aerospace Physiology, Key Laboratory of Aerospace Medicine of Ministry of Education, Fourth Military Medical University, Xi'an, Shaanxi Province, 710032, China.
  • Xu J; Department of Aerospace Physiology, Key Laboratory of Aerospace Medicine of Ministry of Education, Fourth Military Medical University, Xi'an, Shaanxi Province, 710032, China.
  • He SY; Department of Aerospace Physiology, Key Laboratory of Aerospace Medicine of Ministry of Education, Fourth Military Medical University, Xi'an, Shaanxi Province, 710032, China.
  • Cao QL; Department of Aerospace Physiology, Key Laboratory of Aerospace Medicine of Ministry of Education, Fourth Military Medical University, Xi'an, Shaanxi Province, 710032, China.
  • Bai YG; Department of Aerospace Physiology, Key Laboratory of Aerospace Medicine of Ministry of Education, Fourth Military Medical University, Xi'an, Shaanxi Province, 710032, China.
  • Ma J; Department of Aerospace Physiology, Key Laboratory of Aerospace Medicine of Ministry of Education, Fourth Military Medical University, Xi'an, Shaanxi Province, 710032, China.
  • Zhang L; Department of Aerospace Physiology, Key Laboratory of Aerospace Medicine of Ministry of Education, Fourth Military Medical University, Xi'an, Shaanxi Province, 710032, China. lin-july@163.com.
  • Zhou J; Department of Endocrinology, Xijing Hospital, Air Force Medical University, No. 127 Changle West Road, Xi'an, 710032, China. zhoujie@fmmu.edu.cn.
  • Xie MJ; Department of Aerospace Physiology, Key Laboratory of Aerospace Medicine of Ministry of Education, Fourth Military Medical University, Xi'an, Shaanxi Province, 710032, China. xiemanjiang@fmmu.edu.cn.
Apoptosis ; 29(9-10): 1600-1618, 2024 Oct.
Article en En | MEDLINE | ID: mdl-39110356
ABSTRACT
High-altitude pulmonary edema (HAPE) is a fatal threat for sojourners who ascend rapidly without sufficient acclimatization. Acclimatized sojourners and adapted natives are both insensitive to HAPE but have different physiological traits and molecular bases. In this study, based on GSE52209, the gene expression profiles of HAPE patients were compared with those of acclimatized sojourners and adapted natives, with the common and divergent differentially expressed genes (DEGs) and their hub genes identified, respectively. Bioinformatic methodologies for functional enrichment analysis, immune infiltration, diagnostic model construction, competing endogenous RNA (ceRNA) analysis and drug prediction were performed to detect potential biological functions and molecular mechanisms. Next, an array of in vivo experiments in a HAPE rat model and in vitro experiments in HUVECs were conducted to verify the results of the bioinformatic analysis. The enriched pathways of DEGs and immune landscapes for HAPE were significantly different between sojourners and natives, and the common DEGs were enriched mainly in the pathways of development and immunity. Nomograms revealed that the upregulation of TNF-α and downregulation of RPLP0 exhibited high diagnostic efficiency for HAPE in both sojourners and natives, which was further validated in the HAPE rat model. The addition of TNF-α and RPLP0 knockdown activated apoptosis signaling in endothelial cells (ECs) and enhanced endothelial permeability. In conclusion, TNF-α and RPLP0 are shared biomarkers and molecular bases for HAPE susceptibility during the acclimatization/adaptation/maladaptation processes in sojourners and natives, inspiring new ideas for predicting and treating HAPE.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas Ribosómicas / Factor de Necrosis Tumoral alfa / Apoptosis / Células Endoteliales / Mal de Altura Límite: Animals / Humans / Male Idioma: En Revista: Apoptosis Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Países Bajos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas Ribosómicas / Factor de Necrosis Tumoral alfa / Apoptosis / Células Endoteliales / Mal de Altura Límite: Animals / Humans / Male Idioma: En Revista: Apoptosis Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Países Bajos