Growth inhibition of vascular smooth muscle cells derived from urokinase receptor (u-PAR)-deficient mice in the presence of carcinoma cells
Autor: | Osamu Matsuo, Hideharu Fukao, Kiyotaka Okada, Shigeru Ueshima |
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Rok vydání: | 2004 |
Předmět: |
MAPK/ERK pathway
medicine.medical_specialty Vascular smooth muscle Melanoma Experimental Receptors Cell Surface Biology Muscle Smooth Vascular Receptors Urokinase Plasminogen Activator Mice chemistry.chemical_compound Cell Line Tumor Internal medicine Plasminogen Activator Inhibitor 1 medicine Animals Receptor Cells Cultured Urokinase Cell growth Hematology musculoskeletal system Urokinase-Type Plasminogen Activator Coculture Techniques Culture Media Urokinase receptor Endocrinology chemistry Culture Media Conditioned Tissue Plasminogen Activator cardiovascular system Mitogen-Activated Protein Kinases Growth inhibition tissues Plasminogen activator Cell Division medicine.drug |
Zdroj: | Thrombosis Research. 113:41-49 |
ISSN: | 0049-3848 |
DOI: | 10.1016/j.thromres.2004.01.008 |
Popis: | The growth rate of vascular smooth muscle cells (VSMCs), which were derived from aorta of mice deficient in the fibrinolytic factors tissue-type plasminogen activator (t-PA(-/-)), urokinase (u-PA(-/-)), u-PA receptor (u-PAR(-/-)) and type 1 plasminogen activator inhibitor (PAI-1(-/-)), as well as wild-type (WT) mice, was investigated in the presence of mouse melanoma cells (B16). In the VSMCs cultured with a basal medium supplemented with 10% fetal calf serum (FCS), there was no difference in the growth rate among the gene-lacking VSMCs and WT VSMCs, indicating that these fibrinolytic factors were not involved in the FCS-mediated cell proliferation. On the other hand, when these VSMCs were cultured with B16 cells in either the mixed culture or a double-chamber, only u-PAR(-/-) VSMCs showed a significantly lower growth rate. In addition, these suppressive effects on u-PAR(-/-) VSMCs were also observed in the presence of B16-derived conditioned medium (B16/CM). The growth rate of all the VSMCs except u-PAR(-/-) VSMCs was increased in the presence of B16/CM. The degree of the increase in cell number was comparable to that obtained with FCS. These effects on growth activity were partially associated with the levels of mitogen-activated protein kinase (MAPK, p42/p44) activity. The findings suggest that u-PAR plays an important role in the proliferative response of VSMCs and that without u-PAR, there is no intracellular signaling for cell proliferation. |
Databáze: | OpenAIRE |
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