TY  - JOUR
AU  - Smiljanić, Katarina
AU  - Obradović, Milan
AU  - Jovanovic, Aleksandra
AU  - Popović-Đorđević, Jelena
AU  - Dobutović, Branislava
AU  - Jevremovic, Danimir
AU  - Marche, Pierre
AU  - Isenovic, Esma R.
PY  - 2014
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/1853
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.
PB  - Springer, Dordrecht
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 and Jovanovic, Aleksandra and Popović-Đorđević, Jelena and Dobutović, Branislava and Jevremovic, Danimir and Marche, Pierre and Isenovic, 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.",
publisher = "Springer, Dordrecht",
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., Jovanovic, A., Popović-Đorđević, J., Dobutović, B., Jevremovic, D., Marche, P.,& Isenovic, E. R.. (2014). Thrombin stimulates VSMC proliferation through an EGFR-dependent pathway: involvement of MMP-2. in Molecular and Cellular Biochemistry
Springer, Dordrecht., 396(1-2), 147-160.
https://doi.org/10.1007/s11010-014-2151-y

Smiljanić K, Obradović M, Jovanovic A, Popović-Đorđević J, Dobutović B, Jevremovic D, Marche P, Isenovic 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, Jovanovic, Aleksandra, Popović-Đorđević, Jelena, Dobutović, Branislava, Jevremovic, Danimir, Marche, Pierre, Isenovic, 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 . .

TY  - JOUR
AU  - Smiljanić, Katarina
AU  - Dobutovic, B.
AU  - Obradović, Milan
AU  - Nikolić, D.
AU  - Marche, P.
AU  - Isenovic, E. R.
PY  - 2011
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/1195
AB  - Cardiovascular disease is the largest single cause of mortality and its major underlying pathology is atherosclerosis. The proliferation of vascular smooth muscle cells (VSMCs) is a key event in the pathogenesis of the various vascular diseases, including atherosclerosis and hypertension. Thrombin (Thr) is involved in the abnormal proliferation of VSMCs associated with atherosclerosis and hypertension. ADAMs (A Disintegrin And Metalloproteinase) are transmembrane metalloproteinases, belonging to the adamalysins group, that are distinct from matrix metalloproteinases (MMPs) in a way as they have an extracellular disintegrin domain and cytoplasmic domain that can associate with intracellular proteins. There is limited knowledge about the presence of ADAM metalloproteinase activity in Thr-induced VSMCs proliferation. Therefore, this review examines recent findings in signaling mechanisms employed by Thr in modulating the regulation of proliferation of VSMCs with particular emphasis on involvement of ADAM 12 which has been identified as an important mediator of VSMCs hypertrophy and vascular diseases. These findings are critical for understanding the role of Thr in vascular biology and vascular diseases.
PB  - Bentham Science Publ Ltd, Sharjah
T2  - Current Medicinal Chemistry
T1  - Involvement of the ADAM 12 in Thrombin-Induced Rat's VSMCs Proliferation
VL  - 18
IS  - 22
SP  - 3382
EP  - 3386
DO  - 10.2174/092986711796504709
ER  - 

@article{
author = "Smiljanić, Katarina and Dobutovic, B. and Obradović, Milan and Nikolić, D. and Marche, P. and Isenovic, E. R.",
year = "2011",
abstract = "Cardiovascular disease is the largest single cause of mortality and its major underlying pathology is atherosclerosis. The proliferation of vascular smooth muscle cells (VSMCs) is a key event in the pathogenesis of the various vascular diseases, including atherosclerosis and hypertension. Thrombin (Thr) is involved in the abnormal proliferation of VSMCs associated with atherosclerosis and hypertension. ADAMs (A Disintegrin And Metalloproteinase) are transmembrane metalloproteinases, belonging to the adamalysins group, that are distinct from matrix metalloproteinases (MMPs) in a way as they have an extracellular disintegrin domain and cytoplasmic domain that can associate with intracellular proteins. There is limited knowledge about the presence of ADAM metalloproteinase activity in Thr-induced VSMCs proliferation. Therefore, this review examines recent findings in signaling mechanisms employed by Thr in modulating the regulation of proliferation of VSMCs with particular emphasis on involvement of ADAM 12 which has been identified as an important mediator of VSMCs hypertrophy and vascular diseases. These findings are critical for understanding the role of Thr in vascular biology and vascular diseases.",
publisher = "Bentham Science Publ Ltd, Sharjah",
journal = "Current Medicinal Chemistry",
title = "Involvement of the ADAM 12 in Thrombin-Induced Rat's VSMCs Proliferation",
volume = "18",
number = "22",
pages = "3382-3386",
doi = "10.2174/092986711796504709"
}

Smiljanić, K., Dobutovic, B., Obradović, M., Nikolić, D., Marche, P.,& Isenovic, E. R.. (2011). Involvement of the ADAM 12 in Thrombin-Induced Rat's VSMCs Proliferation. in Current Medicinal Chemistry
Bentham Science Publ Ltd, Sharjah., 18(22), 3382-3386.
https://doi.org/10.2174/092986711796504709

Smiljanić K, Dobutovic B, Obradović M, Nikolić D, Marche P, Isenovic ER. Involvement of the ADAM 12 in Thrombin-Induced Rat's VSMCs Proliferation. in Current Medicinal Chemistry. 2011;18(22):3382-3386.
doi:10.2174/092986711796504709 .

Smiljanić, Katarina, Dobutovic, B., Obradović, Milan, Nikolić, D., Marche, P., Isenovic, E. R., "Involvement of the ADAM 12 in Thrombin-Induced Rat's VSMCs Proliferation" in Current Medicinal Chemistry, 18, no. 22 (2011):3382-3386,
https://doi.org/10.2174/092986711796504709 . .

TY  - JOUR
AU  - Isenovic, Esma R.
AU  - Fretaud, Maxence
AU  - Dobutović, Branislava
AU  - Sudar, Emina
AU  - Smiljanić, Katarina
AU  - Zarić, Božidarka L.
AU  - Trpkovic, Andreja
AU  - Marche, Pierre
PY  - 2009
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/612
AB  - Insulin (INS) via INS receptor acts as a mitogen in vascular smooth muscle cells (VSMCs) through stimulation of multiple signaling mechanisms, including p42/44 mitogen-activated protein kinase (ERK1/2) and phosphatidyl inositol-3 kinase (PI3K). In addition, cytosolic phospholipase 2 (cPLA(2)) is linked to VSMCs proliferation. However, the upstream mechanisms responsible for activation of cPLA(2) are not well defined. Therefore, this investigation used primary cultured rat VSMCs to examine the role of PI3K and ERK1/2 in the INS-dependent phosphorylation of cPLA(2) and proliferation induced by INS. Exposure of VSMCs to INS (100 nM) for 10 min increased the phosphorylation of cPLA(2) by 1.5-fold (p  lt  0.01), which was blocked by the cPLA(2) inhibitor MAFP (10 mu M; 15 min). Similarly, the PI3K inhibitor LY294002 (10 mu M; 15 min) and ERK1/2 inhibitor PD98059 (20 mu M; 15 min) abolished the INS-mediated increase in cPLA(2) phosphorylation by 59% (p  lt  0.001), and by 75% (p  lt  0.001), respectively. Further, inhibition of cPLA2 with cPLA2 inhibitor MAFP abolished the INS-stimulated ERK1/2 phosphorylation by 65% (p  lt  0.01). Incubation of rat VSMCs with INS resulted in an increase of VSMCs proliferation by 85% (p  lt  0.001). The effect of INS on VSMCs proliferation was significantly (p  lt  0.01) reduced by pretreatment with MAFP. Thus, we hypothesized that INS stimulates VSMCs proliferation via a mechanism involving the PI3K-dependent activation of cPLA(2) and release of arachidonic acid (AA), which activates ERK1/2 and further amplifies cPLA(2) activity. (C) 2009 International Federation for Cell Biology. Published by Elsevier Ltd. All rights reserved.
PB  - Academic Press Ltd- Elsevier Science Ltd, London
T2  - Cell Biology International
T1  - A novel hypothesis regarding the possible involvement of cytosolic phospholipase 2 in insulin-stimulated proliferation of vascular smooth muscle cells
VL  - 33
IS  - 3
SP  - 386
EP  - 392
DO  - 10.1016/j.cellbi.2009.01.010
ER  - 

@article{
author = "Isenovic, Esma R. and Fretaud, Maxence and Dobutović, Branislava and Sudar, Emina and Smiljanić, Katarina and Zarić, Božidarka L. and Trpkovic, Andreja and Marche, Pierre",
year = "2009",
abstract = "Insulin (INS) via INS receptor acts as a mitogen in vascular smooth muscle cells (VSMCs) through stimulation of multiple signaling mechanisms, including p42/44 mitogen-activated protein kinase (ERK1/2) and phosphatidyl inositol-3 kinase (PI3K). In addition, cytosolic phospholipase 2 (cPLA(2)) is linked to VSMCs proliferation. However, the upstream mechanisms responsible for activation of cPLA(2) are not well defined. Therefore, this investigation used primary cultured rat VSMCs to examine the role of PI3K and ERK1/2 in the INS-dependent phosphorylation of cPLA(2) and proliferation induced by INS. Exposure of VSMCs to INS (100 nM) for 10 min increased the phosphorylation of cPLA(2) by 1.5-fold (p  lt  0.01), which was blocked by the cPLA(2) inhibitor MAFP (10 mu M; 15 min). Similarly, the PI3K inhibitor LY294002 (10 mu M; 15 min) and ERK1/2 inhibitor PD98059 (20 mu M; 15 min) abolished the INS-mediated increase in cPLA(2) phosphorylation by 59% (p  lt  0.001), and by 75% (p  lt  0.001), respectively. Further, inhibition of cPLA2 with cPLA2 inhibitor MAFP abolished the INS-stimulated ERK1/2 phosphorylation by 65% (p  lt  0.01). Incubation of rat VSMCs with INS resulted in an increase of VSMCs proliferation by 85% (p  lt  0.001). The effect of INS on VSMCs proliferation was significantly (p  lt  0.01) reduced by pretreatment with MAFP. Thus, we hypothesized that INS stimulates VSMCs proliferation via a mechanism involving the PI3K-dependent activation of cPLA(2) and release of arachidonic acid (AA), which activates ERK1/2 and further amplifies cPLA(2) activity. (C) 2009 International Federation for Cell Biology. Published by Elsevier Ltd. All rights reserved.",
publisher = "Academic Press Ltd- Elsevier Science Ltd, London",
journal = "Cell Biology International",
title = "A novel hypothesis regarding the possible involvement of cytosolic phospholipase 2 in insulin-stimulated proliferation of vascular smooth muscle cells",
volume = "33",
number = "3",
pages = "386-392",
doi = "10.1016/j.cellbi.2009.01.010"
}

Isenovic, E. R., Fretaud, M., Dobutović, B., Sudar, E., Smiljanić, K., Zarić, B. L., Trpkovic, A.,& Marche, P.. (2009). A novel hypothesis regarding the possible involvement of cytosolic phospholipase 2 in insulin-stimulated proliferation of vascular smooth muscle cells. in Cell Biology International
Academic Press Ltd- Elsevier Science Ltd, London., 33(3), 386-392.
https://doi.org/10.1016/j.cellbi.2009.01.010

Isenovic ER, Fretaud M, Dobutović B, Sudar E, Smiljanić K, Zarić BL, Trpkovic A, Marche P. A novel hypothesis regarding the possible involvement of cytosolic phospholipase 2 in insulin-stimulated proliferation of vascular smooth muscle cells. in Cell Biology International. 2009;33(3):386-392.
doi:10.1016/j.cellbi.2009.01.010 .

Isenovic, Esma R., Fretaud, Maxence, Dobutović, Branislava, Sudar, Emina, Smiljanić, Katarina, Zarić, Božidarka L., Trpkovic, Andreja, Marche, Pierre, "A novel hypothesis regarding the possible involvement of cytosolic phospholipase 2 in insulin-stimulated proliferation of vascular smooth muscle cells" in Cell Biology International, 33, no. 3 (2009):386-392,
https://doi.org/10.1016/j.cellbi.2009.01.010 . .