HMGB1 as a potential biomarker and therapeutic target for severe COVID-19.
Identifieur interne : 000673 ( Main/Corpus ); précédent : 000672; suivant : 000674HMGB1 as a potential biomarker and therapeutic target for severe COVID-19.
Auteurs : Ruochan Chen ; Yan Huang ; Jun Quan ; Jiao Liu ; Haichao Wang ; Timothy R. Billiar ; Michael T. Lotze ; Herbert J. Zeh ; Rui Kang ; Daolin TangSource :
- Heliyon [ 2405-8440 ] ; 2020.
Abstract
COVID-19 has attracted global attention due to its rapid spread around the world with substantial morbidity and associated mortality. Severe COVID-19 can be complicated by the acute respiratory distress syndrome, sepsis and septic shock leading to death. These complications are thought to result from an overactivation of the immune system, leading to a cytokine storm syndrome associated with multiple organ failure. Here, we report that high mobility group box 1 (HMGB1), a prototypical damage-associated molecular pattern (DAMP) and a central mediator of lethal inflammation, could be a potential target for innovative therapeutic strategies for COVID-19. Serum HMGB1 in severe COVID-19 patients is elevated (189.40 ± 140.88 ng/ml). Exogenous HMGB1 induces the expression of SARS-CoV-2 entry receptor ACE2 in alveolar epithelial cells in an AGER-dependent manner. Importantly, genetic (using AGER siRNA) or pharmacological (using glycyrrhizin, chloroquine, hydroxychloroquine, and FPS-ZM1) inhibition of the HMGB1-AGER pathway blocks ACE2 expression. Thus, HMGB1 inhibitors are likewise promising drug candidates for the treatment of patients suffering from COVID-19.
DOI: 10.1016/j.heliyon.2020.e05672
PubMed: 33313438
PubMed Central: PMC7720697
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">HMGB1 as a potential biomarker and therapeutic target for severe COVID-19.</title><author><name sortKey="Chen, Ruochan" sort="Chen, Ruochan" uniqKey="Chen R" first="Ruochan" last="Chen">Ruochan Chen</name><affiliation><nlm:affiliation>Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Hunan Key Laboratory of Viral Hepatitis, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.</nlm:affiliation></affiliation></author><author><name sortKey="Huang, Yan" sort="Huang, Yan" uniqKey="Huang Y" first="Yan" last="Huang">Yan Huang</name><affiliation><nlm:affiliation>Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Hunan Key Laboratory of Viral Hepatitis, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.</nlm:affiliation></affiliation></author><author><name sortKey="Quan, Jun" sort="Quan, Jun" uniqKey="Quan J" first="Jun" last="Quan">Jun Quan</name><affiliation><nlm:affiliation>Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Hunan Key Laboratory of Viral Hepatitis, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.</nlm:affiliation></affiliation></author><author><name sortKey="Liu, Jiao" sort="Liu, Jiao" uniqKey="Liu J" first="Jiao" last="Liu">Jiao Liu</name><affiliation><nlm:affiliation>The Third Affiliated Hospital, Guangzhou Medical University, Guangdong 510600, China.</nlm:affiliation></affiliation></author><author><name sortKey="Wang, Haichao" sort="Wang, Haichao" uniqKey="Wang H" first="Haichao" last="Wang">Haichao Wang</name><affiliation><nlm:affiliation>Laboratory of Emergency Medicine, North Shore University Hospital, Feinstein Institute for Medical Research, Manhasset, New York 11030, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Billiar, Timothy R" sort="Billiar, Timothy R" uniqKey="Billiar T" first="Timothy R" last="Billiar">Timothy R. Billiar</name><affiliation><nlm:affiliation>Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania 15219, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Lotze, Michael T" sort="Lotze, Michael T" uniqKey="Lotze M" first="Michael T" last="Lotze">Michael T. Lotze</name><affiliation><nlm:affiliation>Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania 15219, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Zeh, Herbert J" sort="Zeh, Herbert J" uniqKey="Zeh H" first="Herbert J" last="Zeh">Herbert J. Zeh</name><affiliation><nlm:affiliation>Department of Surgery, UT Southwestern Medical Center, Dallas, Texas, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Kang, Rui" sort="Kang, Rui" uniqKey="Kang R" first="Rui" last="Kang">Rui Kang</name><affiliation><nlm:affiliation>Department of Surgery, UT Southwestern Medical Center, Dallas, Texas, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Tang, Daolin" sort="Tang, Daolin" uniqKey="Tang D" first="Daolin" last="Tang">Daolin Tang</name><affiliation><nlm:affiliation>Department of Surgery, UT Southwestern Medical Center, Dallas, Texas, USA.</nlm:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2020">2020</date><idno type="RBID">pubmed:33313438</idno><idno type="pmid">33313438</idno><idno type="doi">10.1016/j.heliyon.2020.e05672</idno><idno type="pmc">PMC7720697</idno><idno type="wicri:Area/Main/Corpus">000673</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">000673</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">HMGB1 as a potential biomarker and therapeutic target for severe COVID-19.</title><author><name sortKey="Chen, Ruochan" sort="Chen, Ruochan" uniqKey="Chen R" first="Ruochan" last="Chen">Ruochan Chen</name><affiliation><nlm:affiliation>Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Hunan Key Laboratory of Viral Hepatitis, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.</nlm:affiliation></affiliation></author><author><name sortKey="Huang, Yan" sort="Huang, Yan" uniqKey="Huang Y" first="Yan" last="Huang">Yan Huang</name><affiliation><nlm:affiliation>Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Hunan Key Laboratory of Viral Hepatitis, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.</nlm:affiliation></affiliation></author><author><name sortKey="Quan, Jun" sort="Quan, Jun" uniqKey="Quan J" first="Jun" last="Quan">Jun Quan</name><affiliation><nlm:affiliation>Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Hunan Key Laboratory of Viral Hepatitis, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.</nlm:affiliation></affiliation></author><author><name sortKey="Liu, Jiao" sort="Liu, Jiao" uniqKey="Liu J" first="Jiao" last="Liu">Jiao Liu</name><affiliation><nlm:affiliation>The Third Affiliated Hospital, Guangzhou Medical University, Guangdong 510600, China.</nlm:affiliation></affiliation></author><author><name sortKey="Wang, Haichao" sort="Wang, Haichao" uniqKey="Wang H" first="Haichao" last="Wang">Haichao Wang</name><affiliation><nlm:affiliation>Laboratory of Emergency Medicine, North Shore University Hospital, Feinstein Institute for Medical Research, Manhasset, New York 11030, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Billiar, Timothy R" sort="Billiar, Timothy R" uniqKey="Billiar T" first="Timothy R" last="Billiar">Timothy R. Billiar</name><affiliation><nlm:affiliation>Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania 15219, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Lotze, Michael T" sort="Lotze, Michael T" uniqKey="Lotze M" first="Michael T" last="Lotze">Michael T. Lotze</name><affiliation><nlm:affiliation>Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania 15219, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Zeh, Herbert J" sort="Zeh, Herbert J" uniqKey="Zeh H" first="Herbert J" last="Zeh">Herbert J. Zeh</name><affiliation><nlm:affiliation>Department of Surgery, UT Southwestern Medical Center, Dallas, Texas, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Kang, Rui" sort="Kang, Rui" uniqKey="Kang R" first="Rui" last="Kang">Rui Kang</name><affiliation><nlm:affiliation>Department of Surgery, UT Southwestern Medical Center, Dallas, Texas, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Tang, Daolin" sort="Tang, Daolin" uniqKey="Tang D" first="Daolin" last="Tang">Daolin Tang</name><affiliation><nlm:affiliation>Department of Surgery, UT Southwestern Medical Center, Dallas, Texas, USA.</nlm:affiliation></affiliation></author></analytic><series><title level="j">Heliyon</title><idno type="ISSN">2405-8440</idno><imprint><date when="2020" type="published">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">COVID-19 has attracted global attention due to its rapid spread around the world with substantial morbidity and associated mortality. Severe COVID-19 can be complicated by the acute respiratory distress syndrome, sepsis and septic shock leading to death. These complications are thought to result from an overactivation of the immune system, leading to a cytokine storm syndrome associated with multiple organ failure. Here, we report that high mobility group box 1 (HMGB1), a prototypical damage-associated molecular pattern (DAMP) and a central mediator of lethal inflammation, could be a potential target for innovative therapeutic strategies for COVID-19. Serum HMGB1 in severe COVID-19 patients is elevated (189.40 ± 140.88 ng/ml). Exogenous HMGB1 induces the expression of SARS-CoV-2 entry receptor ACE2 in alveolar epithelial cells in an AGER-dependent manner. Importantly, genetic (using AGER siRNA) or pharmacological (using glycyrrhizin, chloroquine, hydroxychloroquine, and FPS-ZM1) inhibition of the HMGB1-AGER pathway blocks ACE2 expression. Thus, HMGB1 inhibitors are likewise promising drug candidates for the treatment of patients suffering from COVID-19.</div></front></TEI><pubmed><MedlineCitation Status="PubMed-not-MEDLINE" Owner="NLM"><PMID Version="1">33313438</PMID><DateRevised><Year>2021</Year><Month>02</Month><Day>12</Day></DateRevised><Article PubModel="Electronic-eCollection"><Journal><ISSN IssnType="Print">2405-8440</ISSN><JournalIssue CitedMedium="Print"><Volume>6</Volume><Issue>12</Issue><PubDate><Year>2020</Year><Month>Dec</Month></PubDate></JournalIssue><Title>Heliyon</Title><ISOAbbreviation>Heliyon</ISOAbbreviation></Journal><ArticleTitle>HMGB1 as a potential biomarker and therapeutic target for severe COVID-19.</ArticleTitle><Pagination><MedlinePgn>e05672</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1016/j.heliyon.2020.e05672</ELocationID><Abstract><AbstractText>COVID-19 has attracted global attention due to its rapid spread around the world with substantial morbidity and associated mortality. Severe COVID-19 can be complicated by the acute respiratory distress syndrome, sepsis and septic shock leading to death. These complications are thought to result from an overactivation of the immune system, leading to a cytokine storm syndrome associated with multiple organ failure. Here, we report that high mobility group box 1 (HMGB1), a prototypical damage-associated molecular pattern (DAMP) and a central mediator of lethal inflammation, could be a potential target for innovative therapeutic strategies for COVID-19. Serum HMGB1 in severe COVID-19 patients is elevated (189.40 ± 140.88 ng/ml). Exogenous HMGB1 induces the expression of SARS-CoV-2 entry receptor ACE2 in alveolar epithelial cells in an AGER-dependent manner. Importantly, genetic (using AGER siRNA) or pharmacological (using glycyrrhizin, chloroquine, hydroxychloroquine, and FPS-ZM1) inhibition of the HMGB1-AGER pathway blocks ACE2 expression. Thus, HMGB1 inhibitors are likewise promising drug candidates for the treatment of patients suffering from COVID-19.</AbstractText><CopyrightInformation>© 2020 The Author(s).</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Chen</LastName><ForeName>Ruochan</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Hunan Key Laboratory of Viral Hepatitis, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Huang</LastName><ForeName>Yan</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Hunan Key Laboratory of Viral Hepatitis, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Quan</LastName><ForeName>Jun</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Hunan Key Laboratory of Viral Hepatitis, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Liu</LastName><ForeName>Jiao</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>The Third Affiliated Hospital, Guangzhou Medical University, Guangdong 510600, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wang</LastName><ForeName>Haichao</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>Laboratory of Emergency Medicine, North Shore University Hospital, Feinstein Institute for Medical Research, Manhasset, New York 11030, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Billiar</LastName><ForeName>Timothy R</ForeName><Initials>TR</Initials><AffiliationInfo><Affiliation>Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania 15219, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lotze</LastName><ForeName>Michael T</ForeName><Initials>MT</Initials><AffiliationInfo><Affiliation>Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania 15219, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zeh</LastName><ForeName>Herbert J</ForeName><Initials>HJ</Initials><AffiliationInfo><Affiliation>Department of Surgery, UT Southwestern Medical Center, Dallas, Texas, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kang</LastName><ForeName>Rui</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Department of Surgery, UT Southwestern Medical Center, Dallas, Texas, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Tang</LastName><ForeName>Daolin</ForeName><Initials>D</Initials><AffiliationInfo><Affiliation>Department of Surgery, UT Southwestern Medical Center, Dallas, Texas, USA.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2020</Year><Month>12</Month><Day>07</Day></ArticleDate></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>Heliyon</MedlineTA><NlmUniqueID>101672560</NlmUniqueID><ISSNLinking>2405-8440</ISSNLinking></MedlineJournalInfo><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">COVID-19</Keyword><Keyword MajorTopicYN="N">Cell culture</Keyword><Keyword MajorTopicYN="N">Cell death</Keyword><Keyword MajorTopicYN="N">HMGB1</Keyword><Keyword MajorTopicYN="N">Immunology</Keyword><Keyword MajorTopicYN="N">Infectious disease</Keyword><Keyword MajorTopicYN="N">Inflammation</Keyword><Keyword MajorTopicYN="N">Microbiology</Keyword><Keyword MajorTopicYN="N">Virology</Keyword></KeywordList><CoiStatement>The authors declare no conflict of interest.</CoiStatement></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2020</Year><Month>07</Month><Day>01</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2020</Year><Month>08</Month><Day>26</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2020</Year><Month>12</Month><Day>03</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2020</Year><Month>12</Month><Day>14</Day><Hour>11</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2020</Year><Month>12</Month><Day>15</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2020</Year><Month>12</Month><Day>15</Day><Hour>6</Hour><Minute>1</Minute></PubMedPubDate></History><PublicationStatus>epublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">33313438</ArticleId><ArticleId IdType="doi">10.1016/j.heliyon.2020.e05672</ArticleId><ArticleId IdType="pii">S2405-8440(20)32515-9</ArticleId><ArticleId IdType="pmc">PMC7720697</ArticleId></ArticleIdList><ReferenceList><Reference><Citation>Nature. 2020 Mar;579(7798):270-273</Citation><ArticleIdList><ArticleId IdType="pubmed">32015507</ArticleId></ArticleIdList></Reference><Reference><Citation>Science. 1999 Jul 9;285(5425):248-51</Citation><ArticleIdList><ArticleId IdType="pubmed">10398600</ArticleId></ArticleIdList></Reference><Reference><Citation>Lancet. 2020 Mar 28;395(10229):1015-1018</Citation><ArticleIdList><ArticleId 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