TNF-α and RPLP0 drive the apoptosis of endothelial cells and increase susceptibility to high-altitude pulmonary edema
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 gen...
Gespeichert in:
| Veröffentlicht in: | Apoptosis (London) 2024-10, Vol.29 (9-10), p.1600-1618 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 1618 |
|---|---|
| container_issue | 9-10 |
| container_start_page | 1600 |
| container_title | Apoptosis (London) |
| container_volume | 29 |
| creator | 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 |
| description | 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. |
| doi_str_mv | 10.1007/s10495-024-02005-9 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_11416372</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>3089882514</sourcerecordid><originalsourceid>FETCH-LOGICAL-c356t-2a50c4ed833c679a10e1fa3aeb25d7ede5746f125a175dc01bc689c1b74bd3553</originalsourceid><addsrcrecordid>eNp9kc1u1TAQhSMEoqXwAiyQJTZsAjNxHCcrhCoKSFdQoSKxsxx7cq-rJA62c6U-Fi_CM-H2lvKzYGHZ8nxzfManKJ4ivEQA-Soi1J0ooarzAhBld684RiF52Ujx9X4-8wbKFltxVDyK8RIAeMvrh8UR7xCBi-a42F98PCt_fGd6tuzz-eYcmA1uTyztiOnFL8lHF5kfGM3W58vR6ZEZGsd40-JmE0hHYnGNhpbkeje6dMWSZzu33ZV6TC6tltiyjpOfdbhiZGnSj4sHgx4jPbndT4ovZ28vTt-Xm0_vPpy-2ZQmu0tlpQWYmmzLuWlkpxEIB8019ZWwMisJWTcDVkKjFNYA9qZpO4O9rHvLheAnxeuD7rL2E1lDcwp6VEtwU_aivHbq78rsdmrr9wqxxobLKiu8uFUI_ttKManJxesP0DP5NSoObde2lcA6o8__QS_9GuY8n-IIUlRtUzeZqg6UCT7GQMOdGwR1nas65KpyruomV9Xlpmd_znHX8ivIDPADEHNp3lL4_fZ_ZH8C37-wZA</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>3107528646</pqid></control><display><type>article</type><title>TNF-α and RPLP0 drive the apoptosis of endothelial cells and increase susceptibility to high-altitude pulmonary edema</title><source>SpringerLink Journals - AutoHoldings</source><creator>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</creator><creatorcontrib>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</creatorcontrib><description>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.</description><identifier>ISSN: 1360-8185</identifier><identifier>ISSN: 1573-675X</identifier><identifier>EISSN: 1573-675X</identifier><identifier>DOI: 10.1007/s10495-024-02005-9</identifier><identifier>PMID: 39110356</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Acclimatization ; Altitude ; Altitude acclimatization ; Apoptosis ; Biochemistry ; Biological effects ; Biomarkers ; Biomedical and Life Sciences ; Biomedicine ; Cancer Research ; Cell Biology ; Diagnostic systems ; Edema ; Endothelial cells ; Enrichment ; Functionals ; Gene expression ; Gene set enrichment analysis ; Genes ; High altitude ; High-altitude environments ; In vivo methods and tests ; Molecular modelling ; Oncology ; Tumor necrosis factor-α ; Virology</subject><ispartof>Apoptosis (London), 2024-10, Vol.29 (9-10), p.1600-1618</ispartof><rights>The Author(s) 2024</rights><rights>2024. The Author(s).</rights><rights>The Author(s) 2024. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>The Author(s) 2024 2024</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c356t-2a50c4ed833c679a10e1fa3aeb25d7ede5746f125a175dc01bc689c1b74bd3553</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s10495-024-02005-9$$EPDF$$P50$$Gspringer$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s10495-024-02005-9$$EHTML$$P50$$Gspringer$$Hfree_for_read</linktohtml><link.rule.ids>230,314,776,780,881,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39110356$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ge, Yi-Ling</creatorcontrib><creatorcontrib>Li, Pei-Jie</creatorcontrib><creatorcontrib>Bu, Ying-Rui</creatorcontrib><creatorcontrib>Zhang, Bin</creatorcontrib><creatorcontrib>Xu, Jin</creatorcontrib><creatorcontrib>He, Si-Yuan</creatorcontrib><creatorcontrib>Cao, Qing-Lin</creatorcontrib><creatorcontrib>Bai, Yun-Gang</creatorcontrib><creatorcontrib>Ma, Jin</creatorcontrib><creatorcontrib>Zhang, Lin</creatorcontrib><creatorcontrib>Zhou, Jie</creatorcontrib><creatorcontrib>Xie, Man-Jiang</creatorcontrib><title>TNF-α and RPLP0 drive the apoptosis of endothelial cells and increase susceptibility to high-altitude pulmonary edema</title><title>Apoptosis (London)</title><addtitle>Apoptosis</addtitle><addtitle>Apoptosis</addtitle><description>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.</description><subject>Acclimatization</subject><subject>Altitude</subject><subject>Altitude acclimatization</subject><subject>Apoptosis</subject><subject>Biochemistry</subject><subject>Biological effects</subject><subject>Biomarkers</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cancer Research</subject><subject>Cell Biology</subject><subject>Diagnostic systems</subject><subject>Edema</subject><subject>Endothelial cells</subject><subject>Enrichment</subject><subject>Functionals</subject><subject>Gene expression</subject><subject>Gene set enrichment analysis</subject><subject>Genes</subject><subject>High altitude</subject><subject>High-altitude environments</subject><subject>In vivo methods and tests</subject><subject>Molecular modelling</subject><subject>Oncology</subject><subject>Tumor necrosis factor-α</subject><subject>Virology</subject><issn>1360-8185</issn><issn>1573-675X</issn><issn>1573-675X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><recordid>eNp9kc1u1TAQhSMEoqXwAiyQJTZsAjNxHCcrhCoKSFdQoSKxsxx7cq-rJA62c6U-Fi_CM-H2lvKzYGHZ8nxzfManKJ4ivEQA-Soi1J0ooarzAhBld684RiF52Ujx9X4-8wbKFltxVDyK8RIAeMvrh8UR7xCBi-a42F98PCt_fGd6tuzz-eYcmA1uTyztiOnFL8lHF5kfGM3W58vR6ZEZGsd40-JmE0hHYnGNhpbkeje6dMWSZzu33ZV6TC6tltiyjpOfdbhiZGnSj4sHgx4jPbndT4ovZ28vTt-Xm0_vPpy-2ZQmu0tlpQWYmmzLuWlkpxEIB8019ZWwMisJWTcDVkKjFNYA9qZpO4O9rHvLheAnxeuD7rL2E1lDcwp6VEtwU_aivHbq78rsdmrr9wqxxobLKiu8uFUI_ttKManJxesP0DP5NSoObde2lcA6o8__QS_9GuY8n-IIUlRtUzeZqg6UCT7GQMOdGwR1nas65KpyruomV9Xlpmd_znHX8ivIDPADEHNp3lL4_fZ_ZH8C37-wZA</recordid><startdate>20241001</startdate><enddate>20241001</enddate><creator>Ge, Yi-Ling</creator><creator>Li, Pei-Jie</creator><creator>Bu, Ying-Rui</creator><creator>Zhang, Bin</creator><creator>Xu, Jin</creator><creator>He, Si-Yuan</creator><creator>Cao, Qing-Lin</creator><creator>Bai, Yun-Gang</creator><creator>Ma, Jin</creator><creator>Zhang, Lin</creator><creator>Zhou, Jie</creator><creator>Xie, Man-Jiang</creator><general>Springer US</general><general>Springer Nature B.V</general><scope>C6C</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QL</scope><scope>7QP</scope><scope>7TK</scope><scope>7TM</scope><scope>7U9</scope><scope>C1K</scope><scope>H94</scope><scope>K9.</scope><scope>M7N</scope><scope>U9A</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20241001</creationdate><title>TNF-α and RPLP0 drive the apoptosis of endothelial cells and increase susceptibility to high-altitude pulmonary edema</title><author>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</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c356t-2a50c4ed833c679a10e1fa3aeb25d7ede5746f125a175dc01bc689c1b74bd3553</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Acclimatization</topic><topic>Altitude</topic><topic>Altitude acclimatization</topic><topic>Apoptosis</topic><topic>Biochemistry</topic><topic>Biological effects</topic><topic>Biomarkers</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cancer Research</topic><topic>Cell Biology</topic><topic>Diagnostic systems</topic><topic>Edema</topic><topic>Endothelial cells</topic><topic>Enrichment</topic><topic>Functionals</topic><topic>Gene expression</topic><topic>Gene set enrichment analysis</topic><topic>Genes</topic><topic>High altitude</topic><topic>High-altitude environments</topic><topic>In vivo methods and tests</topic><topic>Molecular modelling</topic><topic>Oncology</topic><topic>Tumor necrosis factor-α</topic><topic>Virology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ge, Yi-Ling</creatorcontrib><creatorcontrib>Li, Pei-Jie</creatorcontrib><creatorcontrib>Bu, Ying-Rui</creatorcontrib><creatorcontrib>Zhang, Bin</creatorcontrib><creatorcontrib>Xu, Jin</creatorcontrib><creatorcontrib>He, Si-Yuan</creatorcontrib><creatorcontrib>Cao, Qing-Lin</creatorcontrib><creatorcontrib>Bai, Yun-Gang</creatorcontrib><creatorcontrib>Ma, Jin</creatorcontrib><creatorcontrib>Zhang, Lin</creatorcontrib><creatorcontrib>Zhou, Jie</creatorcontrib><creatorcontrib>Xie, Man-Jiang</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Apoptosis (London)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ge, Yi-Ling</au><au>Li, Pei-Jie</au><au>Bu, Ying-Rui</au><au>Zhang, Bin</au><au>Xu, Jin</au><au>He, Si-Yuan</au><au>Cao, Qing-Lin</au><au>Bai, Yun-Gang</au><au>Ma, Jin</au><au>Zhang, Lin</au><au>Zhou, Jie</au><au>Xie, Man-Jiang</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>TNF-α and RPLP0 drive the apoptosis of endothelial cells and increase susceptibility to high-altitude pulmonary edema</atitle><jtitle>Apoptosis (London)</jtitle><stitle>Apoptosis</stitle><addtitle>Apoptosis</addtitle><date>2024-10-01</date><risdate>2024</risdate><volume>29</volume><issue>9-10</issue><spage>1600</spage><epage>1618</epage><pages>1600-1618</pages><issn>1360-8185</issn><issn>1573-675X</issn><eissn>1573-675X</eissn><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.</abstract><cop>New York</cop><pub>Springer US</pub><pmid>39110356</pmid><doi>10.1007/s10495-024-02005-9</doi><tpages>19</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1360-8185 |
| ispartof | Apoptosis (London), 2024-10, Vol.29 (9-10), p.1600-1618 |
| issn | 1360-8185 1573-675X 1573-675X |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_11416372 |
| source | SpringerLink Journals - AutoHoldings |
| subjects | Acclimatization Altitude Altitude acclimatization Apoptosis Biochemistry Biological effects Biomarkers Biomedical and Life Sciences Biomedicine Cancer Research Cell Biology Diagnostic systems Edema Endothelial cells Enrichment Functionals Gene expression Gene set enrichment analysis Genes High altitude High-altitude environments In vivo methods and tests Molecular modelling Oncology Tumor necrosis factor-α Virology |
| title | TNF-α and RPLP0 drive the apoptosis of endothelial cells and increase susceptibility to high-altitude pulmonary edema |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-03T12%3A46%3A26IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=TNF-%CE%B1%20and%20RPLP0%20drive%20the%20apoptosis%20of%20endothelial%20cells%20and%20increase%20susceptibility%20to%20high-altitude%20pulmonary%20edema&rft.jtitle=Apoptosis%20(London)&rft.au=Ge,%20Yi-Ling&rft.date=2024-10-01&rft.volume=29&rft.issue=9-10&rft.spage=1600&rft.epage=1618&rft.pages=1600-1618&rft.issn=1360-8185&rft.eissn=1573-675X&rft_id=info:doi/10.1007/s10495-024-02005-9&rft_dat=%3Cproquest_pubme%3E3089882514%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=3107528646&rft_id=info:pmid/39110356&rfr_iscdi=true |