Ginkgo biloba Induces Thrombomodulin Expression and Tissue-Type Plasminogen Activator Secretion via the Activation of Krüppel-Like Factor 2 within Endothelial Cells.
Identifieur interne : 000200 ( Main/Corpus ); précédent : 000199; suivant : 000201Ginkgo biloba Induces Thrombomodulin Expression and Tissue-Type Plasminogen Activator Secretion via the Activation of Krüppel-Like Factor 2 within Endothelial Cells.
Auteurs : Yi-Lin Chiu ; Wei-Che Tsai ; Chih-Hsien Wu ; Chun-Hsien Wu ; Cheng-Chung Cheng ; Wei-Shing Lin ; Tsung-Neng Tsai ; Lian-Shan WuSource :
- The American journal of Chinese medicine [ 1793-6853 ] ; 2020.
English descriptors
- KwdEn :
- Cells, Cultured (MeSH), Endothelial Cells (metabolism), Gene Expression (drug effects), Humans (MeSH), Kruppel-Like Transcription Factors (genetics), Kruppel-Like Transcription Factors (metabolism), Plant Extracts (pharmacology), Thrombomodulin (genetics), Thrombomodulin (metabolism), Tissue Plasminogen Activator (genetics), Tissue Plasminogen Activator (metabolism).
- MESH :
- chemical , genetics : Kruppel-Like Transcription Factors, Thrombomodulin, Tissue Plasminogen Activator.
- drug effects : Gene Expression.
- metabolism : Endothelial Cells, Kruppel-Like Transcription Factors, Thrombomodulin, Tissue Plasminogen Activator.
- chemical , pharmacology : Plant Extracts.
- Cells, Cultured, Humans.
Abstract
The effects of thrombo-prevention, such as antiplatelet and anticoagulant activity, have been reported with the usage of Ginkgo biloba extract (GbE); however, the detailed mechanism has not yet been fully investigated, especially the role of Krüppel-like factor 2 (KLF2). This study aimed to investigate whether GbE can activate KLF2 and then induce thrombomodulin (TM) and tissue-type plasminogen activator (t-PA) secretion to enhance the effects of thrombo-prevention. Different concentrations of GbE were incubated with human umbilical vein endothelial cells (HUVECs) to evaluate its effect on endothelial cells. We found that KLF2 expression is correlated to the risk of atherosclerosis and venous thromboembolism in clinical practice. In the HUVEC cell model, GbE stimulated the expression of KLF2 in a dose-dependent manner. Moreover, TM and t-PA secretion increased when the cells were cultured with GbE. Both the expressions and activities of TM and t-PA in the GbE-treated cells declined after KLF2 was blocked by shKLF2. In sum, with GbE treatment, KLF2 expression in human endothelial cells was significantly activated, which in turn induced an increase in the protein expression and activity of TM and t-PA. After shRNA inhibited the KLF2 expression, GbE stopped inducing the expression and activity of TM and t-PA. These findings suggest that GbE exerts an antithrombotic effect on endothelial cells by increasing the TM expression and t-PA secretion; further, KLF2 is a key factor in this mechanism.
DOI: 10.1142/S0192415X20500184
PubMed: 32108493
Links to Exploration step
pubmed:32108493Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en"><i>Ginkgo biloba</i> Induces Thrombomodulin Expression and Tissue-Type Plasminogen Activator Secretion via the Activation of Krüppel-Like Factor 2 within Endothelial Cells.</title><author><name sortKey="Chiu, Yi Lin" sort="Chiu, Yi Lin" uniqKey="Chiu Y" first="Yi-Lin" last="Chiu">Yi-Lin Chiu</name><affiliation><nlm:affiliation>Department of Biochemistry, National Defense Medical Center, Taipei 114, Taiwan, R.O.C.</nlm:affiliation></affiliation></author><author><name sortKey="Tsai, Wei Che" sort="Tsai, Wei Che" uniqKey="Tsai W" first="Wei-Che" last="Tsai">Wei-Che Tsai</name><affiliation><nlm:affiliation>Division of Cardiology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan, R.O.C.</nlm:affiliation></affiliation></author><author><name sortKey="Wu, Chih Hsien" sort="Wu, Chih Hsien" uniqKey="Wu C" first="Chih-Hsien" last="Wu">Chih-Hsien Wu</name><affiliation><nlm:affiliation>Department of Biochemistry, National Defense Medical Center, Taipei 114, Taiwan, R.O.C.</nlm:affiliation></affiliation></author><author><name sortKey="Wu, Chun Hsien" sort="Wu, Chun Hsien" uniqKey="Wu C" first="Chun-Hsien" last="Wu">Chun-Hsien Wu</name><affiliation><nlm:affiliation>Division of Cardiology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan, R.O.C.</nlm:affiliation></affiliation></author><author><name sortKey="Cheng, Cheng Chung" sort="Cheng, Cheng Chung" uniqKey="Cheng C" first="Cheng-Chung" last="Cheng">Cheng-Chung Cheng</name><affiliation><nlm:affiliation>Department of Biochemistry, National Defense Medical Center, Taipei 114, Taiwan, R.O.C.</nlm:affiliation></affiliation></author><author><name sortKey="Lin, Wei Shing" sort="Lin, Wei Shing" uniqKey="Lin W" first="Wei-Shing" last="Lin">Wei-Shing Lin</name><affiliation><nlm:affiliation>Department of Biochemistry, National Defense Medical Center, Taipei 114, Taiwan, R.O.C.</nlm:affiliation></affiliation></author><author><name sortKey="Tsai, Tsung Neng" sort="Tsai, Tsung Neng" uniqKey="Tsai T" first="Tsung-Neng" last="Tsai">Tsung-Neng Tsai</name><affiliation><nlm:affiliation>Department of Biochemistry, National Defense Medical Center, Taipei 114, Taiwan, R.O.C.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Division of Cardiology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan, R.O.C.</nlm:affiliation></affiliation></author><author><name sortKey="Wu, Lian Shan" sort="Wu, Lian Shan" uniqKey="Wu L" first="Lian-Shan" last="Wu">Lian-Shan Wu</name><affiliation><nlm:affiliation>Division of Cardiology, Department of Internal Medicine, Hualien Armed Forces General Hospital, Hualien County 971, Taiwan, R.O.C.</nlm:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2020">2020</date><idno type="RBID">pubmed:32108493</idno><idno type="pmid">32108493</idno><idno type="doi">10.1142/S0192415X20500184</idno><idno type="wicri:Area/Main/Corpus">000200</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">000200</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en"><i>Ginkgo biloba</i> Induces Thrombomodulin Expression and Tissue-Type Plasminogen Activator Secretion via the Activation of Krüppel-Like Factor 2 within Endothelial Cells.</title><author><name sortKey="Chiu, Yi Lin" sort="Chiu, Yi Lin" uniqKey="Chiu Y" first="Yi-Lin" last="Chiu">Yi-Lin Chiu</name><affiliation><nlm:affiliation>Department of Biochemistry, National Defense Medical Center, Taipei 114, Taiwan, R.O.C.</nlm:affiliation></affiliation></author><author><name sortKey="Tsai, Wei Che" sort="Tsai, Wei Che" uniqKey="Tsai W" first="Wei-Che" last="Tsai">Wei-Che Tsai</name><affiliation><nlm:affiliation>Division of Cardiology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan, R.O.C.</nlm:affiliation></affiliation></author><author><name sortKey="Wu, Chih Hsien" sort="Wu, Chih Hsien" uniqKey="Wu C" first="Chih-Hsien" last="Wu">Chih-Hsien Wu</name><affiliation><nlm:affiliation>Department of Biochemistry, National Defense Medical Center, Taipei 114, Taiwan, R.O.C.</nlm:affiliation></affiliation></author><author><name sortKey="Wu, Chun Hsien" sort="Wu, Chun Hsien" uniqKey="Wu C" first="Chun-Hsien" last="Wu">Chun-Hsien Wu</name><affiliation><nlm:affiliation>Division of Cardiology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan, R.O.C.</nlm:affiliation></affiliation></author><author><name sortKey="Cheng, Cheng Chung" sort="Cheng, Cheng Chung" uniqKey="Cheng C" first="Cheng-Chung" last="Cheng">Cheng-Chung Cheng</name><affiliation><nlm:affiliation>Department of Biochemistry, National Defense Medical Center, Taipei 114, Taiwan, R.O.C.</nlm:affiliation></affiliation></author><author><name sortKey="Lin, Wei Shing" sort="Lin, Wei Shing" uniqKey="Lin W" first="Wei-Shing" last="Lin">Wei-Shing Lin</name><affiliation><nlm:affiliation>Department of Biochemistry, National Defense Medical Center, Taipei 114, Taiwan, R.O.C.</nlm:affiliation></affiliation></author><author><name sortKey="Tsai, Tsung Neng" sort="Tsai, Tsung Neng" uniqKey="Tsai T" first="Tsung-Neng" last="Tsai">Tsung-Neng Tsai</name><affiliation><nlm:affiliation>Department of Biochemistry, National Defense Medical Center, Taipei 114, Taiwan, R.O.C.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Division of Cardiology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan, R.O.C.</nlm:affiliation></affiliation></author><author><name sortKey="Wu, Lian Shan" sort="Wu, Lian Shan" uniqKey="Wu L" first="Lian-Shan" last="Wu">Lian-Shan Wu</name><affiliation><nlm:affiliation>Division of Cardiology, Department of Internal Medicine, Hualien Armed Forces General Hospital, Hualien County 971, Taiwan, R.O.C.</nlm:affiliation></affiliation></author></analytic><series><title level="j">The American journal of Chinese medicine</title><idno type="eISSN">1793-6853</idno><imprint><date when="2020" type="published">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Cells, Cultured (MeSH)</term><term>Endothelial Cells (metabolism)</term><term>Gene Expression (drug effects)</term><term>Humans (MeSH)</term><term>Kruppel-Like Transcription Factors (genetics)</term><term>Kruppel-Like Transcription Factors (metabolism)</term><term>Plant Extracts (pharmacology)</term><term>Thrombomodulin (genetics)</term><term>Thrombomodulin (metabolism)</term><term>Tissue Plasminogen Activator (genetics)</term><term>Tissue Plasminogen Activator (metabolism)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Kruppel-Like Transcription Factors</term><term>Thrombomodulin</term><term>Tissue Plasminogen Activator</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Gene Expression</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Endothelial Cells</term><term>Kruppel-Like Transcription Factors</term><term>Thrombomodulin</term><term>Tissue Plasminogen Activator</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Plant Extracts</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Cells, Cultured</term><term>Humans</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The effects of thrombo-prevention, such as antiplatelet and anticoagulant activity, have been reported with the usage of Ginkgo biloba extract (GbE); however, the detailed mechanism has not yet been fully investigated, especially the role of Krüppel-like factor 2 (KLF2). This study aimed to investigate whether GbE can activate KLF2 and then induce thrombomodulin (TM) and tissue-type plasminogen activator (t-PA) secretion to enhance the effects of thrombo-prevention. Different concentrations of GbE were incubated with human umbilical vein endothelial cells (HUVECs) to evaluate its effect on endothelial cells. We found that KLF2 expression is correlated to the risk of atherosclerosis and venous thromboembolism in clinical practice. In the HUVEC cell model, GbE stimulated the expression of KLF2 in a dose-dependent manner. Moreover, TM and t-PA secretion increased when the cells were cultured with GbE. Both the expressions and activities of TM and t-PA in the GbE-treated cells declined after KLF2 was blocked by shKLF2. In sum, with GbE treatment, KLF2 expression in human endothelial cells was significantly activated, which in turn induced an increase in the protein expression and activity of TM and t-PA. After shRNA inhibited the KLF2 expression, GbE stopped inducing the expression and activity of TM and t-PA. These findings suggest that GbE exerts an antithrombotic effect on endothelial cells by increasing the TM expression and t-PA secretion; further, KLF2 is a key factor in this mechanism.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">32108493</PMID><DateCompleted><Year>2020</Year><Month>08</Month><Day>27</Day></DateCompleted><DateRevised><Year>2020</Year><Month>08</Month><Day>27</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1793-6853</ISSN><JournalIssue CitedMedium="Internet"><Volume>48</Volume><Issue>2</Issue><PubDate><Year>2020</Year></PubDate></JournalIssue><Title>The American journal of Chinese medicine</Title><ISOAbbreviation>Am J Chin Med</ISOAbbreviation></Journal><ArticleTitle><i>Ginkgo biloba</i> Induces Thrombomodulin Expression and Tissue-Type Plasminogen Activator Secretion via the Activation of Krüppel-Like Factor 2 within Endothelial Cells.</ArticleTitle><Pagination><MedlinePgn>357-372</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1142/S0192415X20500184</ELocationID><Abstract><AbstractText>The effects of thrombo-prevention, such as antiplatelet and anticoagulant activity, have been reported with the usage of Ginkgo biloba extract (GbE); however, the detailed mechanism has not yet been fully investigated, especially the role of Krüppel-like factor 2 (KLF2). This study aimed to investigate whether GbE can activate KLF2 and then induce thrombomodulin (TM) and tissue-type plasminogen activator (t-PA) secretion to enhance the effects of thrombo-prevention. Different concentrations of GbE were incubated with human umbilical vein endothelial cells (HUVECs) to evaluate its effect on endothelial cells. We found that KLF2 expression is correlated to the risk of atherosclerosis and venous thromboembolism in clinical practice. In the HUVEC cell model, GbE stimulated the expression of KLF2 in a dose-dependent manner. Moreover, TM and t-PA secretion increased when the cells were cultured with GbE. Both the expressions and activities of TM and t-PA in the GbE-treated cells declined after KLF2 was blocked by shKLF2. In sum, with GbE treatment, KLF2 expression in human endothelial cells was significantly activated, which in turn induced an increase in the protein expression and activity of TM and t-PA. After shRNA inhibited the KLF2 expression, GbE stopped inducing the expression and activity of TM and t-PA. These findings suggest that GbE exerts an antithrombotic effect on endothelial cells by increasing the TM expression and t-PA secretion; further, KLF2 is a key factor in this mechanism.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Chiu</LastName><ForeName>Yi-Lin</ForeName><Initials>YL</Initials><AffiliationInfo><Affiliation>Department of Biochemistry, National Defense Medical Center, Taipei 114, Taiwan, R.O.C.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Tsai</LastName><ForeName>Wei-Che</ForeName><Initials>WC</Initials><AffiliationInfo><Affiliation>Division of Cardiology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan, R.O.C.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wu</LastName><ForeName>Chih-Hsien</ForeName><Initials>CH</Initials><AffiliationInfo><Affiliation>Department of Biochemistry, National Defense Medical Center, Taipei 114, Taiwan, R.O.C.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wu</LastName><ForeName>Chun-Hsien</ForeName><Initials>CH</Initials><AffiliationInfo><Affiliation>Division of Cardiology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan, R.O.C.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cheng</LastName><ForeName>Cheng-Chung</ForeName><Initials>CC</Initials><AffiliationInfo><Affiliation>Department of Biochemistry, National Defense Medical Center, Taipei 114, Taiwan, R.O.C.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lin</LastName><ForeName>Wei-Shing</ForeName><Initials>WS</Initials><AffiliationInfo><Affiliation>Department of Biochemistry, National Defense Medical Center, Taipei 114, Taiwan, R.O.C.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Tsai</LastName><ForeName>Tsung-Neng</ForeName><Initials>TN</Initials><AffiliationInfo><Affiliation>Department of Biochemistry, National Defense Medical Center, Taipei 114, Taiwan, R.O.C.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Division of Cardiology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan, R.O.C.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wu</LastName><ForeName>Lian-Shan</ForeName><Initials>LS</Initials><AffiliationInfo><Affiliation>Division of Cardiology, Department of Internal Medicine, Hualien Armed Forces General Hospital, Hualien County 971, Taiwan, R.O.C.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2020</Year><Month>02</Month><Day>28</Day></ArticleDate></Article><MedlineJournalInfo><Country>Singapore</Country><MedlineTA>Am J Chin Med</MedlineTA><NlmUniqueID>7901431</NlmUniqueID><ISSNLinking>0192-415X</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C096161">KLF2 protein, human</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D051741">Kruppel-Like Transcription Factors</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D010936">Plant Extracts</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D018180">Thrombomodulin</NameOfSubstance></Chemical><Chemical><RegistryNumber>19FUJ2C58T</RegistryNumber><NameOfSubstance UI="C063170">Ginkgo biloba extract</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 3.4.21.68</RegistryNumber><NameOfSubstance UI="D010959">Tissue Plasminogen Activator</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D002478" MajorTopicYN="N">Cells, Cultured</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D042783" MajorTopicYN="N">Endothelial Cells</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D015870" MajorTopicYN="N">Gene Expression</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D051741" MajorTopicYN="N">Kruppel-Like Transcription Factors</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D010936" MajorTopicYN="N">Plant Extracts</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D018180" MajorTopicYN="N">Thrombomodulin</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D010959" MajorTopicYN="N">Tissue Plasminogen Activator</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">Endothelial Cells</Keyword><Keyword MajorTopicYN="N">Ginkgo Biloba Extract</Keyword><Keyword MajorTopicYN="N">Krüppel-Like Factor 2</Keyword><Keyword MajorTopicYN="N">Thrombomodulin</Keyword><Keyword MajorTopicYN="N">Thrombosis</Keyword><Keyword MajorTopicYN="N">Tissue-Type Plasminogen Activator</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="pubmed"><Year>2020</Year><Month>2</Month><Day>29</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2020</Year><Month>8</Month><Day>28</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2020</Year><Month>2</Month><Day>29</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">32108493</ArticleId><ArticleId IdType="doi">10.1142/S0192415X20500184</ArticleId></ArticleIdList></PubmedData></pubmed></record>Pour manipuler ce document sous Unix (Dilib)
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