TY  - JOUR
AU  - Smiljanić, Katarina
AU  - Obradović, Milan M.
AU  - Jovanović, Aleksandra
AU  - Đorđević, Jelena D.
AU  - Dobutović, Branislava
AU  - Jevremovic, Danimir
AU  - Marche, Pierre
AU  - Isenović, Esma R.
PY  - 2014
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/134
AB  - 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 LT 0.001) increase of ERK1/2 phosphorylation by 8.7 +/- A 0.9-fold, EGFR phosphorylation by 8.5 +/- A 1.3-fold (p LT 0.001) and DNA synthesis by 3.6 +/- A 0.4-fold (p LT 0.001). Separate 30-min pretreatments with EGFR tyrosine kinase irreversible inhibitor, 10 A mu M PD169540 (PD), and 20 A mu M 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 A mu M 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.
T2  - Molecular and Cellular Biochemistry
T1  - Thrombin stimulates VSMC proliferation through an EGFR-dependent pathway: involvement of MMP-2
VL  - 396
IS  - 1-2
SP  - 147
EP  - 160
DO  - 10.1007/s11010-014-2151-y
ER  - 

@article{
author = "Smiljanić, Katarina and Obradović, Milan M. and Jovanović, Aleksandra and Đorđević, Jelena D. and Dobutović, Branislava and Jevremovic, Danimir and Marche, Pierre and Isenović, Esma R.",
year = "2014",
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 LT 0.001) increase of ERK1/2 phosphorylation by 8.7 +/- A 0.9-fold, EGFR phosphorylation by 8.5 +/- A 1.3-fold (p LT 0.001) and DNA synthesis by 3.6 +/- A 0.4-fold (p LT 0.001). Separate 30-min pretreatments with EGFR tyrosine kinase irreversible inhibitor, 10 A mu M PD169540 (PD), and 20 A mu M 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 A mu M 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.",
journal = "Molecular and Cellular Biochemistry",
title = "Thrombin stimulates VSMC proliferation through an EGFR-dependent pathway: involvement of MMP-2",
volume = "396",
number = "1-2",
pages = "147-160",
doi = "10.1007/s11010-014-2151-y"
}

Smiljanić, K., Obradović, M. M., Jovanović, A., Đorđević, J. D., Dobutović, B., Jevremovic, D., Marche, P.,& Isenović, E. R.. (2014). Thrombin stimulates VSMC proliferation through an EGFR-dependent pathway: involvement of MMP-2. in Molecular and Cellular Biochemistry, 396(1-2), 147-160.
https://doi.org/10.1007/s11010-014-2151-y

Smiljanić K, Obradović MM, Jovanović A, Đorđević JD, Dobutović B, Jevremovic D, Marche P, Isenović ER. Thrombin stimulates VSMC proliferation through an EGFR-dependent pathway: involvement of MMP-2. in Molecular and Cellular Biochemistry. 2014;396(1-2):147-160.
doi:10.1007/s11010-014-2151-y .

Smiljanić, Katarina, Obradović, Milan M., Jovanović, Aleksandra, Đorđević, Jelena D., Dobutović, Branislava, Jevremovic, Danimir, Marche, Pierre, Isenović, Esma R., "Thrombin stimulates VSMC proliferation through an EGFR-dependent pathway: involvement of MMP-2" in Molecular and Cellular Biochemistry, 396, no. 1-2 (2014):147-160,
https://doi.org/10.1007/s11010-014-2151-y . .