Please use this identifier to cite or link to this item:
https://biore.bio.bg.ac.rs/handle/123456789/185
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Smiljanić, Katarina | en_US |
dc.contributor.author | Obradović, Milan | en_US |
dc.contributor.author | Jovanović, Aleksandra | en_US |
dc.contributor.author | Đorđević, Jelena | en_US |
dc.contributor.author | Dobutović, Branislava | en_US |
dc.contributor.author | Jevremović, Danimir | en_US |
dc.contributor.author | Marche, Pierre | en_US |
dc.contributor.author | Isenović, Esma | en_US |
dc.date.accessioned | 2019-06-27T10:05:56Z | - |
dc.date.available | 2019-06-27T10:05:56Z | - |
dc.date.issued | 2014-01-01 | - |
dc.identifier.issn | 0300-8177 | - |
dc.identifier.uri | https://biore.bio.bg.ac.rs/handle/123456789/185 | - |
dc.description.abstract | In 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.iso | en | en_US |
dc.relation.ispartof | Molecular and Cellular Biochemistry | en_US |
dc.subject | Atherosclerosis | en_US |
dc.subject | EGFR transactivation | en_US |
dc.subject | Heparin-binding epidermal growth factor like | en_US |
dc.subject | Matrix metalloproteinase | en_US |
dc.subject | MMP-2 | en_US |
dc.subject | Pathological VSMC proliferation | en_US |
dc.subject | Thrombin signaling cascade | en_US |
dc.title | Thrombin stimulates VSMC proliferation through an EGFR-dependent pathway: Involvement of MMP-2 | en_US |
dc.type | Article | en_US |
dc.identifier.doi | 10.1007/s11010-014-2151-y | - |
dc.identifier.pmid | 25047892 | - |
dc.identifier.scopus | 2-s2.0-84907593049 | - |
dc.identifier.url | https://api.elsevier.com/content/abstract/scopus_id/84907593049 | - |
item.languageiso639-1 | en | - |
item.cerifentitytype | Publications | - |
item.openairetype | Article | - |
item.fulltext | No Fulltext | - |
item.grantfulltext | none | - |
item.openairecristype | http://purl.org/coar/resource_type/c_18cf | - |
crisitem.author.dept | Chair of Comparative Physiology and Ecophysiology | - |
crisitem.author.orcid | 0000-0002-6510-1027 | - |
Appears in Collections: | Journal Article |
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.