Please use this identifier to cite or link to this item: https://biore.bio.bg.ac.rs/handle/123456789/185
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dc.contributor.authorSmiljanić, Katarinaen_US
dc.contributor.authorObradović, Milanen_US
dc.contributor.authorJovanović, Aleksandraen_US
dc.contributor.authorĐorđević, Jelenaen_US
dc.contributor.authorDobutović, Branislavaen_US
dc.contributor.authorJevremović, Danimiren_US
dc.contributor.authorMarche, Pierreen_US
dc.contributor.authorIsenović, Esmaen_US
dc.date.accessioned2019-06-27T10:05:56Z-
dc.date.available2019-06-27T10:05:56Z-
dc.date.issued2014-01-01-
dc.identifier.issn0300-8177-
dc.identifier.urihttps://biore.bio.bg.ac.rs/handle/123456789/185-
dc.description.abstractIn this study, the role of epidermal growth factor receptor (EGFR), extracellular signal-regulated kinase (ERK1/2), heparin-binding EGF-like growth factor (HB-EGF), general metalloproteinases, matrix metalloproteinases-2 (MMP-2) in mediating the mitogenic action of thrombin in rat vascular smooth muscle cells (VSMC) was investigated. The incubation of rat VSMC with thrombin (1 U/ml) for 5 min resulted in significant (p < 0.001) increase of ERK1/2 phosphorylation by 8.7 ± 0.9-fold, EGFR phosphorylation by 8.5 ± 1.3-fold (p < 0.001) and DNA synthesis by 3.6 ± 0.4-fold (p < 0.001). Separate 30-min pretreatments with EGFR tyrosine kinase irreversible inhibitor, 10 μM PD169540 (PD), and 20 μM anti-HB-EGF antibody significantly reduced thrombin-stimulated EGFR and ERK1/2 phosphorylation by 81, 72 % and by 48 and 61 %, respectively. Furthermore, the same pretreatments with PD or anti-HB-EGF antibody reduced thrombin-induced VSMC proliferation by 44 and 45 %, respectively. In addition, 30-min pretreatments with 10 μM specific MMP-2 inhibitor significantly reduced thrombin-stimulated phosphorylation of both EGFR and ERK1/2 by 25 %. Moreover, the same pretreatment with MMP-2 inhibitor reduced thrombin-induced VSMC proliferation by 45 %. These results show that the thrombin-induced DNA synthesis correlates with the level of ERK1/2 activation rather than EGFR activation. These results further suggest that thrombin acts through EGFR and ERK 1/2 signaling pathways involving MMP-2 to upregulate proliferation of VSMC.en_US
dc.language.isoenen_US
dc.relation.ispartofMolecular and Cellular Biochemistryen_US
dc.subjectAtherosclerosisen_US
dc.subjectEGFR transactivationen_US
dc.subjectHeparin-binding epidermal growth factor likeen_US
dc.subjectMatrix metalloproteinaseen_US
dc.subjectMMP-2en_US
dc.subjectPathological VSMC proliferationen_US
dc.subjectThrombin signaling cascadeen_US
dc.titleThrombin stimulates VSMC proliferation through an EGFR-dependent pathway: Involvement of MMP-2en_US
dc.typeArticleen_US
dc.identifier.doi10.1007/s11010-014-2151-y-
dc.identifier.pmid25047892-
dc.identifier.scopus2-s2.0-84907593049-
dc.identifier.urlhttps://api.elsevier.com/content/abstract/scopus_id/84907593049-
item.languageiso639-1en-
item.cerifentitytypePublications-
item.openairetypeArticle-
item.fulltextNo Fulltext-
item.grantfulltextnone-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
crisitem.author.deptChair of Comparative Physiology and Ecophysiology-
crisitem.author.orcid0000-0002-6510-1027-
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